Search

Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.

Canas L, Bayes B, Granada ML, Ibernon M, Porrini E, Benitez R, Diaz JM, Lauzurica R, Moreso F, Torres A, Lampreabe I, Serra A, Romero R. Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation? Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01490.x. © 2011 John Wiley & Sons A/S. Abstract: The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). Methods: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50 ± 13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Results: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14–27) μg/mL. An inverse correlation was found between ADP and HOMA index (r = −0.432; p 0.6 mm had more AGH (p = 0.012) and lower ADP levels (p = 0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. Conclusions: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Background/Aims: Statins are prescribed in kidney transplant recipients in order to manage dyslipidemia, a common complication in these patients. The efficacy of statins in reducing cholesterol levels has been accompanied by pleiotropic effects. Fifty-four kidney transplant patients were included in the present study, the objective of which was to ascertain the effect of 12 weeks of atorvastatin therapy (10 mg/day) on the patients’ lipid profile, renal function, markers of inflammation and plasma peptide profile. Methods: Biochemical variables were determined with a routine clinical laboratory analyzer, and the proteomic approach was based on magnetic particle-assisted sample processing coupled to mass spectrometry readout. Results: Atorvastatin therapy improved the lipid profile of patients and caused significant changes in their plasma peptide profile; peptides with m/z 1063 and 1898 decreased after treatment and were identified as fragments derived from molecules involved in vascular inflammation, i.e. high-molecular-weight kininogen and complement factor C4, respectively. Conclusion: These findings may contribute to the growing body of evidence of the anti-inflammatory actions attributed to statins, by which these drugs could improve these patients’ clinical status.

Background. Insulin-resistance hyperinsulinemia is a novel risk factor for renal disease in the general population. Glomerular hyperfiltration has been proposed as an early consequence of hyperinsulinemia. Methods. In this multicenter cohort study, we analyzed 202 patients without diabetes before or after renal transplantation during the first posttransplant year. Insulin was measured at 3 and 12 months. The majority of patients (91%) were on calcineurin inhibitors. Patients were classified as with persistent normo or hyperinsulinemia when situated below or above the median value of insulin (3 months: 9 mu U/mL; 12 months: 8.74 mu U/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3-12 months Delta CrCL) was calculated. Results. Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months Delta CrCL compared with those with persistent normoinsulinemia (12% [-20/40] vs. -0.03% [-12/18], P=0.035). We performed a multivariate linear regression analysis with the 3 to 12 months Delta CrCL as the dependent variable and different factors that may induce hyperfiltration, including persistent hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor for increased CrCL (beta 0.09, 95% CI 0.07/0.12, P=0.035). Conclusion. In nondiabetic recipients during the first posttransplant year, hyperinsulinemia induced increments in CrCL. As this may herald future renal dysfunction, hyperinsulinemia should not be ignored as a potential target in this population.

Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention.

Proteinuria and dyslipidemia are nonimmune risk factors implicated in the deterioration of kidney function and associated with an increased risk of accelerated atherogenesis. Statin therapy, used for cholesterol reduction, has shown a renoprotective effect in animal models, particularly in cases of proteinuria. This may occur through lipid-independent mechanisms, such as improved endothelial dysfunction/vascular biology, reduced inflammatory cytokine production (transforming growth factor-beta 1 [TGF-beta1]), and regulation of fibrogenic responses. We studied mechanisms of action of agents, such as statins, to change proteinuria, inflammatory parameters, and TGF-beta1 plasma levels in relation to vascular tone.Fifty-six kidney transplant recipients (30 men and 26 women of overall mean age 54 +/- 13 years) were treated posttransplantation with atorvastatin (10 mg/d) for 12 weeks without renin-angiotensin-system blockade drugs. Inflammatory variables, biochemical parameters, lipid profile, renal function, and TGF-beta1 levels were determined at baseline and at 3 months. Vascular stiffness was evaluated using pulse wave velocity (PWV).Baseline TGF-beta1 plasma levels were higher among transplant recipients than healthy controls, namely 8.12 ng/mL (range, 5.82-13.12) to 2.55 (range, 1.78- 4.35) (P.01). Furthermore, the levels remained higher after the treatment with atorvastatin, namely, 7.59 (range, 4.97-12.35) to 2.55 (range, 1.78-4.35) ng/mL (P.01). Atorvastatin treatment significantly decreased total cholesterol as well as low-density lipoprotein cholesterol plasma levels, but did not modify mean blood pressure (MBP), proteinuria, creatinine clearance, or inflammatory factors. Reduction in TGF-beta1 plasma levels was statistically significant among patients with PWV9.75 (m/s) (pathology reference value) namely, from 10.7 ng/mL (range, 7.02-13.98) to 6.7 (range, 3.96-11.94) (P = .038). Among older patients, atorvastatin significantly decrease TGF-beta1 plasma levels: from 9.5 ng/mL (range, 6.45-14.44) to 5.65 (range, 3.63-9.48; P.05). The decreased TGF-beta1 was not related to changes in lipid profiles.Atorvastatin (10 mg/d) improved the lipid profile and moreover among older patients with worse PWV (9.75 m/s), TGF-beta1 levels were significantly reduced. Our results suggested that statins displayed potent actions distinct from their hypolipidemic effects.

BACKGROUND The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Introduction. Various studies describe the pleiotropic antiinflammatory and antioxidant effects of atorvastatin, in addition to its hypolipemic effects. It has been suggested that statins modify glucose homeostasis via their antiinflammatory effects. A further hypothesis suggests that the incidence of posttransplantation diabetes is lower in statin-treated patients. This study sought to ascertain whether atorvastatin modifies glucose homeostasis, adiponectin, and inflammatory markers in kidney transplant recipients. Patients and Methods. Sixty-eight kidney transplant recipients (41 men, 27 women; mean age, 53 ± 12 years) with stable renal function and dyslipidemia were treated with atorvastatin (10 mg/d) for 12 weeks. Glucose, insulin, homeostasis model assessment (HOMA-IR) index, adiponectin, tumor necrosis factor (TNF)-a, and serum C-reactive protein (CRP) concentrations were determined at baseline and at 3 months. The lipid profile, renal function parameters (creatinine, creatinine clearance, and proteinuria), as well as GOT, GPT, and CK were determined at baseline and at 3 months. Results. Treatment with atorvastatin achieved a statistically significant decrease in lipid profile. After 3 months of treatment, 74.6% of patients had total cholesterol and 78.7% low-density lipoprotein (LDL) cholesterol concentrations within reference range (

Background New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT. Methods A total of 68 KTx patients were studied [mean age, 48 +/- 11 years; 70% males; body mass index (BMI), 25 +/- 3 kg/m]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay. Results NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11-22.7) microIU/mL; non-NODAT, 10.05 (7.45-18.4) microIU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49-5.75); non-NODAT, 2.63 (1.52-4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2-11.38) microg/mL; non-NODAT, 11.4 (8.56-15.27) microg/mL, P=0.012]. Inverse correlations between APN and BMI (r=-0.33; P=0.014) and APN and HOMA-IR index (r=-0.39; P=0.002) and between APN and NODAT (r=-0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71-0.96); P=0.01]. Conclusion Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted 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.

Hepcidin is a hormone that regulates the intestinal absorption of iron and its release from the reticuloendothelium. The objective of this study was to determine the use of hepcidin for kidney disease patients with a diagnosis of iron deficiency pretransplantation by evaluating the soluble transferrin receptor (sRTfR-F) index as a marker for iron deficiency. This transverse study of 164 pretransplant patients determined hematometry and conventional markers related to iron metabolism, as well as soluble transferrin receptor (sTfR), its index (sTfR-F), and serum hepcidin concentrations. The following markers of inflammation (MIF) were also assessed C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-alpha), and soluble TNF-alpha receptor (s-TNF-alphaR). Among the studied patients, 11.4% showed an absolute iron deficiency with ferritin concentrations100 ng/mL, a mean hepcidin value of 120.7 +/- 38.5 ng/mL, and a mean sTfR-F value of 1.03 +/- 0.3; 18.2% of patients displayed a ferritin800 ng/mL with mean hepcidin and sTfR-F values of 147.5 +/- 36.6 ng/mL and 0.54 +/- 0.2, respectively. Iron deficiency was not observed in the other patients when considering the conventional markers: ferritin100 ng/mL and transferrin saturation (ST)20%. However, this study showed that determination of hepcidin concentrations together with M/F improved the identification of iron deficiency in pretransplant patients by 21.6%.

The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT).We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria.Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p0.05). Patients with c-IMT0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT.Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

Background. Chronic allograft nephropathy (CAN), a major complication in renal transplant patients, is an important cause of graft loss. Inflammation as measured in the pretransplant and posttransplant phases, using various markers, has been associated with worse renal function and a greater risk of cardiovascular disease and of long-term graft loss. Objective. The objective of our study was to evaluate whether worsening inflammation in the first 3 months postoperatively was a risk factor for developing CAN. Patients and methods. We performed a cross-sectional study in 207 patients. The following markers of inflammation (MIF) were determined pretransplant and at 3 months after grafting: C-reactive protein (CRP) (mg/L), interleukin (IL)-6 (pg/mL), IL-10 (pg/mL), tumor necrosis factor (TNF)-α (pg/mL), and its soluble receptor (ng/mL), soluble-IL2R (UI/mL), pregnancy-associated plasma protein A (PAPP-A; mUI/L), and IL-4 (pg/mL). We also calculated the ratio at 3 months versus the pre value of MIF. Results. CAN was diagnosed after the first year in 23 patients (11.3%) always by renal biopsy performed for clinical indications. Patients with CAN showed worse inflammation, eg, MIF ratios over one, with statistically significant differences for the ratios of TNF-α and PAPP-A (P = .032 and P = .051 respectively). Upon multivariate logistic regression analysis, using CAN as the dependent variable and age, sex, donor age, months on dialysis, acute tubular necrosis, acute rejection, and MIF ratios as covariates, we observed that an acute rejection episode (OR = 13.03; CI = 2.8-60.9; P = .001), CRP ratio (OR = 1.36; CI = 1.07-1.73; P = .013), and PAPP-A ratio (OR = 1.80; CI = 0.92-3.53; P = .005) were independent markers of CAN. Conclusions. Among other factors, inflammation may determine the onset of CAN as diagnosed by renal biopsy.

Background and Objective Disorders in bone mineral metabolism are common after kidney transplantation, covering, among other pathologic conditions, secondary hyperparathyroidism. Paricalcitol, a selective vitamin D receptor activator, is indicated in the prevention and treatment of secondary hyperparathyroidism. Recent evidence suggests that paricalcitol is also associated, by mechanisms not yet clarified, with improved patient survival. To clarify these unknown mechanisms, the aim of this study was to determine whether 3 months of treatment with paricalcitol modified the urinary peptidome of kidney transplant patients. Methods This prospective study included 42 stable kidney transplant patients, randomized in 2 groups: a group treated with 1 μg/d paricalcitol (n = 25) and a control group that did not receive paricalcitol (n = 17). Urine samples of all patients were collected at baseline and after 3 months. The proteomic approach was based on magnetic bead technology coupled to MALDI-TOF mass spectrometry. Results Paricalcitol treatment produced significant changes in urinary peptidome of kidney transplant patients. Variations in urinary peptides were independent of the degree of proteinuria and of the decrease in parathyroid hormone levels. Conclusions With this preliminary study, we obtained a profile of urinary peptides in which changes occurred due to treatment with paricalcitol. The identification of proteins to which these peptides belong may improve our knowledge about the possible pleiotropic effects of paricalcitol.

Statins are prescribed to reduce posttransplant dyslipidemia, which is frequent among kidney graft recipients. Their efficacy to reduce cholesterol levels has been accompanied by pleiotropic effects. Proteomics is the study of the expressed complement of proteins in tissues or biological fluids. It includes the identification of changes in proteins that occur in various states, eg, after drug administration. Our study objectives were: (1) to analyze the effect of atorvastatin (10 mg/d) on lipid profile, renal function, proteinuria, and inflammation parameters, such as C-reactive protein (CRP), and (2) to use proteomics to ascertain whether this treatment modified the patients' urinary peptide profiles seeking to understand the molecular actions of the drug. Urinary peptide profiles, lipids, renal function parameters (creatinine clearance), proteinuria, and CRP were determined in 39 patients at baseline and at 12 weeks after atorvastatin treatment (10 mg/d). The peptide fraction of each sample acquired using magnetic beads was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results showed that treatment with atorvastatin produced a significant reduction in lipid profile, but did not modify renal function (creatinine clearance), proteinuria, or CRP. The proteomic study showed that statin treatment did not produce significant changes in the urinary peptidome, although there was a tendency for some peptides to increase or decrease after the treatment.

Objective Patients on dialysis display increased inflammation (IF) and oxidative stress (OS). Diabetes mellitus (DM) may increase both processes. The role of transplantation in this situation is unknown. Herein we have assessed the evolution of IF and OS following grafting and its relationship to a prior diagnoses of DM and to kidney function at 1 year. Patients and Methods This prospective study included 131 dialysis patients who underwent transplantation of mean age 54 ± 12 years, including 68% men with 19.5% showing prior DM. The following markers of IF and OS were determined prior to and at 3 months after grafting: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), soluble TNFα receptor (sTNFα-R), soluble IL-2 receptor (sIL-2R), oxidized LDL (oxLDL), and anti-oxLDL antibodies (oxLDLab). The evolution (ratio) of these markers was assessed by dividing the values at 3 months by the prior ones. Modification of Diet in Renal Disease (MDRD) was determined at 12 months. Results Patients with prior DM were older ( P = .034). There were no differences in the pregrafting phase between diabetics and nondiabetics in relation to IF or OS. IF and OS showed a worse evolution postgrafting among patients with prior DM. At 1 year postgrafting renal function was greater in patients without prior DM ( P = .022). There was an inverse correlation between the ratios of markers and kidney function at 1 year postgrafting: TNFα: r = −.235 ( P = .012); sIL-2R: r = .441 ( P r = .225 ( P = .017). Conclusions In the pregrafting phase, there were no differences between patients with or without DM in terms of IF and OS. These differences appeared in the postgrafting phase: patients with DM showed greater IF and OS, an increase that may explain the poor kidney function observed at 1 year among patients with DM.

Inflammation plays an important role in the pathogenesis of ischemic acute kidney injury (IAKI). In this study, we hypothesize that transplant recipients with pretransplant inflammation may have a greater chance of developing delayed graft function (DGF), an example of IAKI.We analyzed 178 patients who had undergone their first transplant using cadaveric donors. Blood samples were extracted from transplant recipients prior to transplantation. C-reactive protein (CRP) (nephelometry); interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (automatized enzyme chemiluminescence immunometric assay); and pregnancy-associated plasma protein A (PAPP-A) (enzyme-linked immunosorbent assay) were determined using the pretransplant blood samples. The risk factors analyzed included cold ischemia, type and time of dialysis, donor and recipient age and HLA compatibility.Sixty-one patients (34.3%) developed DGF. Pretransplant TNF-alpha (9.31 +/- 2.57 vs. 10.56 +/- 3.82 pg/mL; p=0.039) and PAPP-A (1.25 +/- 0.74 vs. 1.90 +/- 1.56 mU/L; p=0.002) were significantly elevated in the group of patients with DGF. Univariate analysis showed that PAPP-A, TNF-alpha, cold ischemia, type of dialysis (hemodialysis) and donor age were associated with DGF. Multivariate analysis showed that PAPP-A (p=0.006), cold ischemia (p=0.009) and type of dialysis (p=0.046) were independent risk factors for DGF.Pretransplant inflammation (TNF-alpha, PAPP-A) in transplant recipients could be a risk factor for the development of DGF.

Background Tacrolimus-based immunosuppression, the most widely used regimen in kidney transplantation, increases the risk of new onset diabetes after transplantation (NODAT). However, the prevalence, evolution and risk factors of different prediabetic alterations: impaired fasting glucose, impaired glucose tolerance, and provisional diabetes, have not been established. Methods In this multicenter and prospective study we evaluated 154 nondiabetic kidney transplant recipients receiving tacrolimus, mycophenolate mofetil and low dose steroids. An oral glucose tolerance test was performed 3 and 12 months after transplantation and prediabetes was defined by American Diabetes Association criteria. Results Prediabetes was highly prevalent and showed little variation between 3 and 12 months (36% and 33%, respectively). Impaired glucose tolerance was the most frequent abnormality observed (23% and 25%, respectively) observed. In addition, 20% of recipients showed NODAT by 1 year. Multivariate analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.004-1.14), pretransplant body mass index (OR: 1.3, CI: 1.09-1.6) and triglyceride/high density lipoprotein-cholesterol ratio, a marker of insulin resistance, (OR: 1.4, CI: 1.05-1.9) were independent risk factors for prediabetes. Conclusion One in two recipients with tacrolimus-based immunosuppresion showed prediabetes or NODAT by 1 year posttransplantation when properly investigated. Older age and high pretransplant body mass index and triglyceride/high density lipoprotein-cholesterol ratio were risk factors for prediabetes. These findings may help applying early interventions to prevent the disorder.

Background Renal insufficiency and renal transplant (RT) provoke a microinflammatory state that leads to increased atherosclerosis. It is not fully known whether calcineurin inhibitors (CNIs) play a role in the inflammation observed in these patients or whether any differences exist between CNIs. Objectives The study aimed to establish differences in the inflammatory state of two groups treated with cyclosporine microemulsion (CyA) or tacrolimus (TC). Patients and methods This prospective study included 81 RT patients divided into two groups according to the CNI: CyA group, n = 35 versus TC group, n = 46. The markers of inflammation (MIF) were determined preRT and at 3 and 12 months’ postRT: C-reactive protein (CRP), serum amyloid protein A (SAA), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-α), and pregnancy-associated plasma protein A (PAPP-A). Samples were collected in stable patients in the absence of rejection, active infection, or inflammatory processes. Results No significant differences existed between the markers of inflammation in the two treatment groups prior to transplantation. At 3 months’ posttransplant, patients treated with CyA showed significantly higher levels of IL-6 (P = .05), SAA (P = .03), and sIL-2R (P = .008) compared with patients treated with TC. These differences were maintained for IL-6 (P = .03) and sIL-2R (P = .027) at 12 months’ posttransplant. A multivariate analysis at 3 months showed that only age [OR 10.1; CI (95% 2.6–38.4); P = .001], SAA [OR 4.8; IC (95% 1.4–16.5); P = .015], and sIL-2R [OR 4.9; IC (95% 1.5–16.2); P = .009] were independent predictors of the CNI used. At 12 months, age [OR 3.7; IC (95% 0.9–14.2] and sIL-2R [OR 6.04; IC (95% 1.5–23); P = .006] continued to be independent predictors. Conclusions Patients treated with CyA displayed significantly higher levels of inflammatory markers (IL-6, SAA, sIL-2R) at 3 and 12 months’ posttransplantation, independent of age, gender, time on dialysis, diabetes mellitus (preRT and de novo postRT), and renal function measured by serum creatinine.

The high incidence of new-onset diabetes mellitus after transplantation (NODAT) suggests the need to find new factors to explain the pathogenesis. Our objectives were (1) to confirm that low levels of pre-transplant adiponectin are an independent risk factor for the development of NODAT in a larger transplanted population; (2) to analyze whether adiponectin is a better predictor of NODAT than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age: 53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre-transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A were measured. Forty-five patients developed NODAT. Patients with NODAT had a greater BMI (p = 0.005). Adiponectin was lower (p0.001) and CRP higher (p = 0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin were predictors of NODAT. ROC analysis showed that an adiponectin concentration of 11.4 microg/mL had a significant negative prediction for NODAT risk (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied, adiponectin proved to be an independent predictor of NODAT.

BACKGROUND Cardiovascular disease and chronic allograft nephropathy (CAN) are two of the main complications observed in patients after renal transplantation. Both appear to be manifestations of the same process, in which inflammation plays a determinate role. Pregnancy-associated plasma protein A (PAPP-A) has been shown to be a marker of acute coronary syndrome and cardiovascular pathology. The objective of this study was to demonstrate whether or not serum concentration of pretransplant PAPP-A is a marker of CAN and a predictor of posttransplant cardiovascular events. METHODS In all, 178 renal transplants (65% males; 53+/-12 years of age) followed up over the course of 49.3+/-33.6 months were used in this study. During the follow-up period, 19 patients developed CAN (diagnosed by renal biopsy) and 27 patients had a cardiovascular event. Previous to transplantation, the following were determined: ultrasensitive C-reactive protein (CRP) (nephelometry); interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (immunofluorimetric automatized method), and ultrasensitive PAPP-A (ELISA). RESULTS A positive correlation was found between PAPP-A and the inflammatory markers (PAPP-A vs. CRP, r=0.218; P=0.004; PAPP-A vs. IL-6, r=0.235; P

The increasing prevalence of pre-existing diabetes mellitus (DM) and especially the incidence of post-transplant diabetes mellitus (PTDM) is a disturbing tendency with far-reaching health and cost implications. We assessed the factors associated with PTDM and the impact of either condition on death-censored graft and patient survival.We studied 3365 adult kidney allograft recipients transplanted in 1990, 1994 and 1998, whose graft was functioning after 1 year of follow-up. Three groups were considered: Group I (DM; N = 156), Group II (PTDM; N = 251) and Group III (non-diabetic; N = 2958).Group I patients had been dialysed for shorter periods and received angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blockers (ARB) therapy more frequently during follow-up than the other groups (P0.001). Mean age, body weight and body mass index (BMI) were greater in Group II patients than the other groups (P0.001). Group II showed lower rejection rates than Group III (P0.01). Risk factors for developing PTDM were recipient age60 years (OR = 2.24; P0.001), female recipient (OR = 1.5; P0.005), recipient weight65 kg (OR = 1.77; P0.002), BMI25 kg/m(2) (OR = 1.6; P0.04) or30 kg/m(2) (OR = 2.92; P0.005), and tacrolimus-based therapy (OR = 1.48; P0.05). Of note, the use of Sandimmune vs Neoral had a protective effect (OR = 0.7; P0.01). Using Cox's proportional hazards analysis, DM correlated with reduced death-censored graft survival (RR = 1.68; 95% CI = 1.14-2.47; P0.008), while PTDM correlated with reduced patient survival (RR = 1.55; 95% CI = 1.05-2.27; P0.02).One year after transplantation, DM was associated with a decrease in death-censored graft survival, while PTDM was an independent negative predictor of patient survival after kidney transplantation. New strategies to improve outcome are needed.

IT HAS been known for years that Epstein-Barr virus (EBV) and the development of posttransplant lymphoproliferative disorders (PTLD) are closely related. However, there are few data regarding the evolution of EBVspecific serologic markers as well as their actual clinical relevance in the transplant population. In the immunocompetent patient, serologic diagnosis of EBV infection relies on detecting antibodies against several EBV-specific antigens: viral capsid antigen (VCA), early antigen (EA), and nuclear antigens (EBNA), which appear at different times after infection. Nevertheless, in the immunosuppressed host interpretation of the former serologic antibodies is hampered by the inability of these patients to mount suitable serologic responses. The aims of our study were to (1) prospectively follow-up several EBV serologic markers in kidney transplant (KT) recipients, (2) determine the EBV reactivation rate in this group of patients, and (3) establish their clinical value and correlation with different KT variables.

The aim of the study presented here was to set up and standardize a semiquantitative polymerase chain reaction method for monitoring Epstein-Barr virus (EBV) DNA levels in blood and saliva samples from transplant recipients and to determine the value of these levels as an early marker for the development of post-transplant lymphoproliferative disorders. EBV DNA load was prospectively measured in 53 adult kidney transplant recipients. Results were correlated with clinical features and degree of immunosuppression. Healthy blood donors and patients with infectious mononucleosis were used as controls. Levels higher than 500 EBV DNA copies/75,000 peripheral blood mononuclear cells were found in all patients with infectious mononucleosis and in all patients with post-transplant lymphoproliferative disorder but in only 7.5% of transplant recipients without that complication.

Josep Bonet1, Albert Martinez-Castelao2, Beatriz Bayés11Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 2Department of Nephrology, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona, SpainPurpose: Metabolic syndrome is a cluster of biochemical abnormalities including cardiovascular and diabetes risk factors. The development of diabetes mellitus after renal transplant represents a major posttransplant complication that may adversely affect graft/patient survival. The aim of this study was to assess the role of metabolic syndrome in patients on hemodialysis as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant.Patients and methods: This was a prospective observational epidemiologic study carried out in adult nondiabetic patients undergoing chronic hemodialysis and on the renal transplant waiting list between November 2008 and April 2009. Patients were followed up from Visit 1 (baseline) to 6 months after the renal transplant. The analysis of the role of metabolic syndrome in hemodialysis patients as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant included the estimation of relative risk and its 95% confidence interval (CI).Results: A total of 383 evaluable patients were entered into the study (mean age, 52.7 years; male, 57.7%; Caucasian, 90.1%). The prevalence of metabolic syndrome on hemodialysis was 30.4% (95% CI, 25.8%–35.4%). Hypertension was the most prevalent criterion for metabolic syndrome (65.0%), followed by low levels of high-density lipoprotein cholesterol (52.7%), abdominal obesity (36.2%), hypertriglyceridemia (32.4%), and impaired glucose (8.9%). After the renal transplant, the prevalence of metabolic syndrome was still 25.8%. During the posttransplant period, the incidence of new-onset diabetes mellitus reached 13.0% (95% CI, 7.8%–20.6%) and patients with pretransplant metabolic syndrome were 2.6 times (95% CI, 1.043–6.608) more likely to develop new-onset diabetes mellitus after the renal transplant than those without metabolic syndrome.Conclusion: The presence of metabolic syndrome in patients undergoing hemodialysis represents an independent risk factor for the incidence of new-onset diabetes mellitus after renal transplant.Keywords: dialysis, kidney transplantation, metabolic syndrome X, posttransplant diabetes

Disseminated varicella zoster virus (VZV) infection is a rare complication after renal transplantation in adults. We report 4 cases diagnosed in our transplant patients. One of which was a primary infection (chicken pox) with multivisceral involvement (hepatitis, pneumonitis, myocarditis, and disseminated intravascular coagulation). The other 3 patients VZV-seropositive before transplantation suffered from disseminated zoster. No immunosuppressive drug was significantly associated with a higher risk of disseminated VZV infection. However, from our experience, we believe that mycophenolate mofetil (MMF), plays a part in the clinical presentation of the disease. Early treatment with high doses of acyclovir is fundamental in infection control. It is essential to perform a pretransplantation serological VZV study on all patients.

Background and objectives: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. Method: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Results: Vitamin D deficiency (250HD(3) = 2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100 pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Conclusions: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Antecedentes y objetivos: La relación entre las alteraciones del metabolismo mineral, las fracturas óseas y las calcificaciones vasculares en receptores de un trasplante renal no han sido establecidas. Método: Realizamos un estudio transversal en 727 receptores estables procedentes de 28 centros de trasplante españoles. Se determinaron de manera centralizada los parámetros del metabolismo mineral; también se centralizó la semicuantificación de las fracturas vertebrales y de las calcificaciones de la aorta abdominal. Resultados: La deficiencia de vitamina D (25OHD3 < 15 ng/ml) fue más frecuente en mujeres y en los estadios CKD-T I-III (29, 6 vs. 44, 4%; p = 0, 003). La relación inversa y significativa observada entre los niveles de 25OHD3 y PTH fue modificada por el género de tal manera que la pendiente fue mayor en las mujeres que en los hombres (p = 0, 01). Un 15% de los receptores mostró alguna fractura vertebral (VFx) con un grado de deformidad =2. Los factores relacionados con la VFx diferían en función del género: en los hombres, la edad (OR: 1, 04; IC 95%: 1, 01-1, 06) y el tratamiento con CsA (OR: 3, 2; IC 95: 1, 6-6, 3); en las mujeres la edad (OR: 1, 07; IC 95%: 1, 03-1, 12) y los niveles de PTH (OR per 100 pg/ml increase: 1, 27; IC 95%: 1, 043-1, 542). Las calcificaciones de la aorta abdominal fueron comunes (67, 2%) y se relacionaron con los factores de riesgo clásicos, pero no con los parámetros del metabolismo mineral. Conclusiones: La deficiencia de vitamina D es más frecuente en las mujeres receptoras de un trasplante renal y en los estadios más tempranos de la CKD-T, y es un factor que contribuye al desarrollo de hiperparatiroidismo secundario. Las VFx prevalentes están relacionadas con unos niveles más elevados de PTH solamente en las mujeres.