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Measurement of the vascular resistive index (RI) by Doppler ultrasonography has been proposed as a non-invasive method to evaluate renal allograft dysfunction, but there are conflicting reports about its clinical utility. The aim of our study was to analyse the donor and recipient characteristics related to RI measured at days 2 and 3 after renal transplantation and the relationship between RI and allograft outcome. RI was measured by Doppler ultrasonography in 333 patients at days 2 or 3 post-transplantation. Donor and recipient variables and allograft outcome were collected from a prospectively maintained institutional database. In patients with RI higher than 0.7, donor age, recipient age, duration of renal replacement therapy, incidence of diabetes, hypertension and atherosclerosis in the recipient, pulse pressure, initial creatinine and the incidence of delayed graft function (DGF) were higher. After multivariate analysis, the only variables that remained significant for an increased risk of higher RI were recipient age over 55 years, presence of diabetes in the recipient and DGF. Recipient age, previous diabetes mellitus and DGF are the most important determinants of transplant kidney RI in the first days after transplantation. So both the graft recipient and the graft itself, but not the donor, determine intra-renal Doppler indices. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Mycobacterium xenopi is an unusual pathogen and few such cases have been reported in the literature. We report the case of a patient with a sirolimus-based immunosuppressive regimen, who developed lung cavitation. M. xenopi was isolated from the sputum. The patient was treated initially with rifampicin, isoniazid, and pyrazinamide; levofloxacin was added to the treatment regimen after M. xenopi was demonstrated. A possible relationship between sirolimus and M. xenopi infection has been postulated, probably due to the combination of pulmonary toxicity and cellular immunosuppression of rapamycin. [ABSTRACT FROM AUTHOR]

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Abstract: Carotid arteriosclerosis is a marker of cardiovascular risk in the general population. Cardiovascular disease is highly prevalent in kidney transplant recipients. This study analyzed the impact of arteriosclerotic carotid lesions on the evolution of renal transplant recipients. Methods: This prospective study was performed in 70 patients with renal transplantations (mean age 52 ± 12 years; 67% men (n = 47). High-resolution B-mode ultrasonography (7.5 MHz) of both carotid arteries was performed at baseline to assess carotid caliber, mean and maximum intima-media thickness (IMT), presence of arteriosclerotic plaques (number and maximum height), and percentage stenosis. We analyzed the impact of carotid arteriosclerosis and various donor-recipient clinical covariables on long-term patient and graft survival. Results: Mean follow-up was 9.7 ± 2.5 years (2–14). Atheroma plaques were detected in 74% of patients (n = 52). The mean number of plaques was 3.96 ± 2.88 and maximum plaque height was 2.49 ± 0.97 mm. IMT was 0.71 ± 0.21 mm (0.4–1.5) with 27% of patients (n = 19) having an IMT value greater than 0.8 mm. Sonographic signs of occlusion were evident in 13% (n = 9) and the mean occlusion was 33 ± 11% (range 20%–45%). The presence of plaques was significantly associated with age (P = .002), hypertension and diabetes (P = .016), and hypercholesterolemia (P = .01). There was an association between age and arterial wall thickness (P = .042). Acute rejection was an independent risk factor for graft loss (OR 8.14, P = .003). The multivariate study identified carotid wall thickness as an independent risk factor for patient death (OR 12.7, P = .017). Conclusion: Carotid arteriosclerosis is highly prevalent among renal transplant recipients. Carotid lesions were an independent risk factor for long-term patient death. High-resolution ultrasound imaging of the carotid arteries was a useful, noninvasive diagnostic technique for accurate assessment of cardiovascular risk in renal transplant recipients. [Copyright &y& Elsevier]

Objective: This is a follow-up study of a large, multicentre study that compared tacrolimus and microemulsified cyclosporin A after renal transplantation. A total of 557 patients for primary renal transplantation or retransplantation with low immunological risk (PRA < 50%) had been recruited into the original 6-month study with 286 patients randomized to tacrolimus (Tac) and 271 patients to cyclosporin microemulsion (CyA), concomitantly with steroids and azathioprine. After 6 months, there was a significant difference (p < 0.001) in the incidence of biopsy-proven acute rejection with 19.6% (Tac) and 37.3% (CyA), and biopsy-proven steroid-resistant acute rejection with 9.4% (Tac) and 21.0% (CyA) (Margreiter R, Lancet 359: 741-746, 2003). Methods: All 50 centres were asked to provide follow-up information of all patients whether withdrawn during the main study or not at 1, 2, and 3 years post transplant. Data were entered and analysed by an independent clinical research organisation. Results: At the 3-year follow-up, data were available for 217 (Tac) and 203 (CyA) patients (76.2% of total cohort). Up to the 3-year follow-up 9 patients had died in each group, in the Tac group 25 grafts and in the CyA group 32 grafts were lost since transplantation. Median calculated creatinine clearance was 64.5 mL/min in the Tac group compared with 60.3 mL/min in the CyA group. The incidence of acute rejection between 6 months and 3 years was low in both groups (Tac 15 vs. CyA 17), preserving the difference observed after 6 months. The mean Tac dose was 0.08 mg/kg/day and the mean trough level was 8.5 ng/mL. The mean CyA dose was 2.9 mg/kg/day and the mean trough level was 137.3 ng/mL. Mean blood pressure was similar in both groups (SBP 135.5 vs.138.4 mmHg, DBP 83.2 vs. 83.1 mmHg), however, the use of antihypertensive medication was higher in the CyA group (73.7% vs. 80.7%, p = ns). Despite the significantly higher use of lipid lowering medication (17.5% vs. 32.7%, p < 0.01), the mean cholesterol level was significantly higher (5.13 mmol/L vs. 5.47 mmol/L, p < 0.05) in the CyA group. Use of insulin or of oral antihyperglycaemics was not different between groups at 3-year followup. The administration of MMF differed between the groups (Tac 8.8% vs. CyA 15.8%, p < 0.05). In the Tac group 2.8% and in the CyA group 18.2% of patients had switched their baseline immunosuppressant (p < 0.01). More patients in the CyA group (67.7% vs. 79.3%, p < 0.01) received steroids, the mean doses were 4.9 mg/day (Tac) and 5.5 mg/day (CyA). The overall side effect profile was comparable between groups, however cosmetic adverse effects, and bone disorders were less frequent with tacrolimus treatment. Conclusions: At 3 years post transplantation the advantages of Tac therapy seen in the first 6 months were preserved. There was a tendency towards better graft survival and better renal function in the tacrolimus group. Concomitant medication load, both with regard to immunosuppressive drugs and cardiovascular drugs, was lower in tacrolimus treated patients. [ABSTRACT FROM AUTHOR]

Introduction The 2013 Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline suggests measuring cystatin C (sCys) in adults with glomerular filtration rate (GFR) based on creatinine (sCr) between 45 and 59 mL/min/1.73 m 2 if confirmation of chronic kidney disease (CKD) is required. There is not enough evidence to recommend the use of sCys or sCr to estimate GFR in kidney transplant recipients. Objectives Our aims were to describe the evolution of sCr, sCys, and GFR in a group of kidney transplant patients and to determine their association with some markers of morbidity at 1 year. Methods A total of 54 patients were included. Analytical and clinical data were recorded. Renal function was analyzed using the CKD Epidemiology Collaboration (EPI) sCr equation and CKD-EPI sCys equation. Results sCys-estimated GFR was higher than estimated from sCr by CKD-EPI. The values of sCys have more variability than those of sCr. The agreement between the stages of CKD by sCr or sCys-estimated GFR measured by Cohen's kappa coefficient was only fair. One-year CKD-associated variables correlated differently with sCr and sCys-estimated GFR. Hemoglobin, uric acid, calcium, and phosphorus related to sCr-estimated GFR, whereas serum albumin was associated with sCys-estimated GFR. Conclusions sCys values have a higher variability than sCr in kidney transplant recipients. sCys- or sCr-based GFRs have a nonsimilar behavior in these patients with weak agreement to stratify CKD stages and a different relationship to CKD-related comorbid conditions. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Regulatory T cells (Tregs) have gained an important role in mechanisms of tolerance and protection against the transplant rejection. However, only limited retrospective data have shown a relationship between peripheral blood Tregs and better long-term graft survival. The purpose of the present study was to investigate prospectively circulating Treg levels and their association with long-term graft survival. Methods: Ninety kidney transplant recipients underwent measurement of Treg levels in peripheral blood before as well as at 6 months and 1 year posttransplantation. Receiver operating characteristic curves were applied to test the sensitivity and specificity of Treg levels to predict prognosis. Results: Treg levels before transplantation correlated with those at 6 months and 12 months posttransplantation (P < .001 and P = .002, respectively). Patients who maintained high Treg levels (above 70th percentile) at both 6 and 12 months displayed better long-term graft survival at 4 and 5 years follow-up (P = .04 and P = .043 respectively). There was no effect on patient survival. Conclusion: Detection of high levels of peripheral blood Tregs was associated with better graft survival possibly using as a potential marker of prognosis. [Copyright &y& Elsevier]

Introduction Along with death engraftment, in recent years, antibody-mediated damage has been identified as the leading cause of loss of kidney transplants. Despite the recognition of the role of the B-lymphocyte subpopulation in the development of both tolerance and rejection, little is known about the trigger mechanisms and effectors of this humoral response. Background We analyzed the relationship between B lymphocyte subpopulations and levels of B-cell–activating factor (BAFF) with the histological findings in biopsies of renal transplantation. Material and Methods We selected 35 patients whose kidney transplant biopsy was performed between January and November 2015. The biopsy specimens were classified according to Banff criteria. At the moment of the biopsy BAFF levels and B-lymphocyte subpopulations in blood were measured using enzyme-linked immunosorbent assay (ELISA) and using flow cytometry, respectively. Results Mean BAFF levels were 493 ± 245 pg/mL. The median performance of biopsy post-transplantation was 12.9 (11.7-23.9) months. BAFF levels correlated with pretransplantation antibodies ( r = 0.523; P = .002) but not with kidney function. In biopsies performed more than 1 year after transplantation BAFF levels correlated with the severity of chronic glomerular (cg) involvement ( r = 0.625; P = .003). Histological variables related to antibody-mediated injury selected by principal component analysis (glomerulitis, peritubular capillary, and chronic glomerulopathy) related to BAFF levels (B factor, 116; 95% confidence interval [CI], 12–220; P = .029). Biopsy specimens with transplant glomerulopathy (TG) showed lower levels of circulating naive CD19 + subpopulation, IgD+, and CD27- (32.7 ± 28.1 vs 87.9 ± 79.1; P = .017) compared with biopsy specimens without TG. Conclusions Elevated levels of BAFF are associated with increased presence and severity of TG and a set of variables related to antibody-mediated histological damage. TG is associated with changes in circulating B-lymphocyte subpopulations that could contribute to its pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction The definition of antibody-mediated rejection (AMR) is based on serologic (presence and/or development of donor-specific anti-HLA antibodies [DSAs]) and histologic (C4d deposition and endothelial damage) criteria. However, several cases of AMR have been described without C4d deposition, and other cases of histologic AMR without DSAs, which could be driven by other non-HLA alloantibodies such as anti-MICA or anti-angiotensin II type I receptor (AT1R). Here we studied clinical and histologic humoral rejection in kidney transplant recipients without evidence of anti-HLA antibodies. Materials and Methods Fifteen kidney transplant recipients with AMR defined as C4d + and/or histologic g+ptc without anti-HLA antibodies in screening test were studied. Sera at the moment of biopsy and 2 months earlier were studied for anti-HLA antibodies by Luminex, in neat, diluted 1/160, and sera after treatment with dithiothreitol (DTT) and confirmed by single-antigen test. The anti-AT1R was measured by enzyme-linked immunosorbent assay. Results A lack of anti-HLA and MICA antibodies was confirmed after anti-HLA screening test in all conditions (neat, diluted, and DTT-treated) and de novo development of AT1R antibodies was ruled out. Nevertheless, after single-antigen test, 3 patients were identified with a weak reaction against class I antigen and another 4 patients against class II antigen. Due to the lack of locus-C typing in the donors, the DSA assignment cannot be confirmed, whereas anti-HLA class II antigens were DSA. Conclusions A low sensitivity in the screening of anti-HLA antibody testing was observed. Our results suggest performing single-antigen test in seronegative patients with clinical humoral rejection after screening to confirm the presence of DSA. [ABSTRACT FROM AUTHOR]

Abstract: Due to disparity between organ supply and demand, use of kidneys from suboptimal donors has become increasingly common. Several donor quality systems have been developed to identify kidneys with an increased risk for graft dysfunction and loss. The purpose of our study was to compare the utility of Deceased Donor Score (DDS) and expanded criteria donor (ECD) status to predict kidney transplant outcomes in a single center. We analysed 280 deceased donor renal transplantation procedures, collecting data from the prospectively maintained institutional database. Kidney transplant outcome variable included delayed graft function, 1-year glomerular filtration rate (GFR1y), and death-censored graft loss (DCGL). Kidneys were obtained from marginal donors in 45.7% of transplant recipients by DDS and in 24.9% by ECD. DDS-defined marginal donors suffered delayed graft function (DGF) more frequently than nonmarginal donors (40.8% vs 25.0%; P = .006), whereas ECD did not develop DGF at a greater rate. GFR1Y was significantly worse among patients receiving kidneys from marginal donors: DDS 40.3 ± 12.9 vs 57.7 ± 19.4 mL/min/1.73 m2 (P < .001) and ECD 39.4 ± 14.1 vs 53.8 ± 19.1 mL/min/1.73 m2 (P < .0001). The most severe donor category defined by DDS (grade D) showed an independently worse death-censored graft survival hazard rate [HR] 2.661, 95% confidence interval [CI], 1.076–6.582; P = .034). DDS and ECD scoring systems are based on donor information available at the time of transplantation that predict 1-year graft function. Moreover in our center, DDS was better to predict DGF and death-censored graft survival than ECD. [Copyright &y& Elsevier]

Abstract: Renal transplant recipients are at high risk of cardiovascular disease (CVD). New-onset diabetes mellitus after transplantation (NODAT) contributes to the risk of CVD, reducing graft and patient survival. To improve outcome of kidney transplant recipients, it is of great interest to identify those patients who will develop NODAT. The aim of our study was to explore the predictive value of fifth-day fasting plasma glucose (FPG), third-month proteinuria, and pulse pressure (PP) for NODAT development. We analyzed 282 non-previously-diabetic kidney transplants in our center. Fifth-day FPG, PP, and third-month 24-hour proteinuria were collected. NODAT was defined at month 12 according to the “consensus guidelines”: symptoms of diabetes plus casual glucose concentrations ≥ 200 mg/dL or FPG ≥ 126 mg/dL. Some 46 patients (16.3%) developed NODAT at month 12. Fifth-day FPG (133 ± 35 vs 108 ± 16 mg/dL, P < .001) and PP (57 ± 17 vs 49 ± 15 mm Hg, P = .007) were significantly higher in patients at risk for NODAT, but there was no difference in third-month proteinuria (652 ± 959 vs 472 ± 1336 mg, P = .390). A multivariate regression model showed an increased risk for NODAT associated with recipient age, body mass index, smoking habit, and a fifth-day FPG ≥ 126 mg/dL (relative risk 4.784, 95% confidence interval 2.121–10.788, P = .0002). The negative predictive value of a fifth-day FPG ≥ 126 mg/dL for predicting 1-year NODAT was 89.4%. Fifth-day FPG was independently related to NODAT development. The detection of a fifth-day FPG ≥ 126 mg/dL increases the risk of suffering NODAT more than 4 times. Fifth-day FPG < 126 mg/dL allows us to identify a transplant population with a low risk (near 10%) for NODAT. [Copyright &y& Elsevier]

Abstract: Background: Some transplant recipients demonstrate an inadequate response to erythropoiesis-stimulating agents, or so-called erythropoietin (Epo) resistance. The cause is multifactorial. Resistance to EPO may entail a poor prognosis for the graft and the patient, although results in the literature are inconsistent, and long-term follow-up is lacking. Objective: To evaluate whether the presence of Epo resistance at the beginning of the study was a predictive factor for graft and patient survival. Materials and Methods: From 482 renal transplant recipients (Kidney Disease Outcomes Quality Initiative stage 3–4T) receiving Epo-stimulating agents in the Anemia and Renal Transplantation in Spain study, 101 were selected for the present study. Erythropoietin resistance was defined as a ratio of weekly Epo dosage/hemoglobin concentration >486,94 U/g/dL with a hemoglobin/<11 g/dL. Darbepoetin dosage was calculated in Epo equivalent units, with a 1:200 conversion factor. Patients were grouped as Epo-resistant (ER+) or not Epo-resistant (ER−), to assess whether Epo resistance was predictive of patient and graft survival. Results: There were no differences in demographic data between the 2 groups except for a higher incidence of vascular, interstitial, and diabetes-related causes of chronic renal failure in the ER+ group. At 3 years posttransplantation, graft survival was 33% in the ER+ group vs 58% in the ER− group (P = .06), and patient survival was 52% in the ER+ group vs 88% in the ER− group (P = .008). Using a Cox regression model, at 3 years, the relative risk of graft failure was 1.96 in the ER+ group (95% CI, 0.93–3.12; P = .07), and of patient death was 3.9 (95% confidence interval, 1.30–11.63; P = .01). Conclusion: Erythropoietin resistance is an independent risk factor for death after renal transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Studies of allotolerance in animal models do not usually consider the presence of preexisting memory T cells and activated immune status. However, humans are exposed throughout life to a multitude of external agents that enhance the immune memory. In this article, we consider the effect that a previous kidney transplant has on the number of regulatory T cells (Tregs), effector memory T cells (TEM), and central memory T cells (TCM). Sixty-three patients with end-stage renal disease were studied just before being transplanted (51 first transplants and 12 retransplants). The numbers of Tregs (CD4+ CD25highCD127lowCD27+CD62L+CD45RO+FOXP3+), TEM (CD3+CD45RO+CD62L+), and TCM (CD3+CD45RO+CD62L−) cell subsets were quantified in peripheral blood by flow cytometry. The absolute number of Tregs was slightly lower in patients with previous allografts (median, 95% confidence interval [CI]: 16.7 cells/mm3, 12–20.5) than in those who received their first transplants (median, 95% CI: 19.6 cells/mm3, 19.3–29.6; P-NS). Clearer differences were found with the number of CD3+ TCM, since the transplanted patients had lower numbers (238 cells/mm3, 153–323) than those who had not yet received transplants (378 cells/mm3, 317–439; P = .029). As a result, the TEM/TCM ratios of both CD4+ and CD8+ T cells in patients with previous allografts were higher than in those who received first transplants. In conclusion, the assessment of just the number of Tregs in renal transplant patients is not enough and must be read together with the number of TEM and TCM. The TEM:TCM ratio increases in patients with previous allografts, probably due to activation of the immune response in renal transplantation. [Copyright &y& Elsevier]

Abstract: Plasma cell dyscrasias can cause renal disease. Sensitive methods have recently been introduced to quantify serum free light chains (sFLCs). Renal function may influence the variability of these methods, as shown in chronic kidney disease (CKD) patients, but this problem has not been widely addressed in renal transplant patients. Herein, we examined the association between polyclonal sFLC concentrations and renal function among a population of renal transplant patients. We studied 102 kidney allograft recipients and 53 CKD patients classified according to KDOQI (Kidney Disease Outcomes Quality Initiative) stages. None of them had been diagnosed with monoclonal gammopathy. sFLCs were quantified by nephelometry. Both serum κ and λ free light chain concentrations rose progressively through each stage of KDOQI among both transplant and nontransplant patients (P < .0001). In the former setting, sFLC concentrations significantly correlated, using a Spearman coefficient, with serum creatinine, and serum cystatin concentrations as well as estimated glomerular filtration rate: namely, 0.723, 0.797, and −0.711 for sκFLC and 0.705, 0.759, and −0.694 for sλFLC, respectively (P < .0001 in all cases). Spearman correlation coefficients in nontransplant patients were: 0.559, 0.848, and −0.766 for sκFLC and 0.702, 0.875, and −0.855 for sλFLC, respectively (P < .0001 in all cases). In conclusion, sFLCs must be interpreted cautiously due to their clear association with renal function. Therefore, renal transplantation did not produce changes that were different from those dependent on renal function. [ABSTRACT FROM AUTHOR]

Abstract: Objective: There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Patients and Methods: Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Results: Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). Conclusions: Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination. [Copyright &y& Elsevier]

Abstract: Introduction: Infection remains a significant cause of morbidity and mortality after solid organ transplantation. Genetic background has an influence on the incidence of infection. The aim of our study was to analyze the relationship between cytokine polymorphisms and infection in our kidney transplant recipients. Methods: DNA from 255 kidney transplant recipients was isolated routinely. Polymerase chain reaction sequence-specific primer was performed using commercially available cytokine genotyping primer packs to determine polymorphisms of interleukin (IL)-10, transforming growth factor-beta, tumor necrosis factor-alpha, interferon-gamma, IL-6, IL-4, IL-2, IL-12, IL-4R alpha, IL-1RA, IL-1R, IL-1 beta, and IL-1 alpha. The appearance and number of infections within the first year after transplantation were identified retrospectively. Results: One hundred twenty-two patients experienced at least one episode of infection in the first year after transplant. The frequency of the −511 IL-1β CC genotype and the frequencies of the −1188 IL-12 CA and CC genotypes were significantly higher among the infected patients compared with the noninfected patients. We failed to observe significant differences in the genotype distribution of the other analyzed cytokines regarding the incidence of infection. After adjusting, recipient IL-1β (−511 CC) genotype (relative risk [RR] 2.67, 95% confidence interval (CI) 1.30 to 5.49, P = .007) and recipient IL-12 (−1188 CA and CC) genotypes (RR 2.57, 95% CI 1.22 to 5.38, P = .012) predicted independently the risk of infection in the first year after kidney transplantation. Conclusion: Kidney transplant recipients with −511 IL-1β CC genotype or with −1188 IL-12 CA and CC genotypes were at higher risk of developing infections in the first year after transplantation. Patients with genetic susceptibility to infection may benefit from less potent immunosuppressive therapy and more intense preventive measures. [Copyright &y& Elsevier]

Abstract: Everolimus has recently been introduced into clinical practice with promising perspectives due to its efficacy, lack of nephrotoxicity, and antitumor effects. Experience in clinical trials associated with low-dose cyclosporine showed good results, but there is almost no experience in calcineurin inhibitor (CNI) elimination learning it as the primary immunosuppressant. We describe our experience in a series of 78 stable renal transplant patients who were switched to Everolimus with complete and quick elimination of the CNI: the procedure of conversion, pharmacokinetic results after conversion, evolution of renal parameters (renal function, proteinuria, and others), and safety data (acute rejection and adverse events). An initial dose of 3 mg/d was adequate to obtain the recommended trough levels between 5 and 10 ng/mL. Our results demonstrated that conversion to Everolimus was a simple, safe procedure that must be considered in patients CNI toxicity, especially those with malignant neoplasms and progressive deterioration of renal function due to chronic allograft nephropathy. [Copyright &y& Elsevier]

Abstract: Purpose: We investigated the effects of acute maximal hydratation with hemoce (H) and dextran-40 (D40) on the postoperative graft function, following renal transplantation (RT) in a canine model. Methods: After induction of anesthesia with pentobarbital (5 mg/kg), 18 beagle dogs were randomized to receive either saline solution to increase the central venous pressure (CVP) to 5 mm Hg (GI); H solution to increase the CVP to 10 mm Hg (GII); or D40 to achieve 15 mm Hg (GIII), before reperfusion. A pulmonary artery catheter was used to measure CVP, mean pulmonary artery pressure, and cardiac output (CO). The surgical procedure consisted of autotransplantation of the dog’s left kidney an hour prior to cold ischemia with University of Wisconsin solution, followed by contralateral nephrectomy. Diuresis, creatinine (Cr), and BUN levels were measure at 24 hours before RT, as well as 24, 48, and 72 hours after the procedure. Results: Only in the treated groups did cardiac filling presures and CO increase as a result of hydration. Only in the GI group did serum Cr and blood urea nitrogen significantly peak at the second postoperative day while it continued to increase at two (GII) and three (GIII) times greater than GI on the third day. Histological examination showed osmotic nephrosis like-lesions only among treated grafts. Conclusion: We concluded that maximal hydration with H and D40 colloid deteriorated postoperative graft function after RT. We believe that in the future the effects of any colloid solution should be tested in an animal model in the fashion as we have described, in order to know which one, and at what dose, is the safest to improve kidney allograft outcome. [Copyright &y& Elsevier]

Abstract: Conversion to mammalian target of rapamycin inhibitors (mTORi) is an ever more frequent practice in renal transplant recipients, even if it is not always satisfactory, needing to be suspended for various reasons in certain patients. We analyzed the evolution of proteinuria as a marker of kidney damage after withdrawal of mTORi for any reason in order to assess conversion failure risk. Among 1633 renal transplant patients with 185 converted to mTORi, we considered the 52 (28%) who withdrew as result of intolerance or a bad evolution after at least 3 months use (median: 142 days after conversion). Four groups were defined according to the evolution of proteinuria: group 1 (G1), stable after conversion; group 2 (G2), increased with complete recovery (<1 g); group 3 (G3), increased with partial recovery (>1 g); or group 4 (G4), increased without recovery. The evolution according to the groups was: G1 (57.1%), G2 (17.2%), G3 (5.7%), and G4 (20%). There were no differences between the good (G1 and G2) and the bad evolution groups (G3 and G4) in proteinuria at the time of conversion (838 ± 641 vs 532 ± 404 mg/d) or renal function (1.95 ± 0.47 vs 1.90 ± 0.4 mg/dL). Six months after withdrawal, proteinuria was stable in G1 and G2 but worse in G3 and G4 (781 ± 643 vs 4479 ± 3235 mg/d); the same observation was noted for renal failure (2.1 ± 0.71 vs 2.8 ± 1.57 mg/dL). Among about 75% of patients in whom mTORi was withdrawn, no injury remained in the medium term whereas among the other 25%, there was a residual injury. [Copyright &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Antiphospholipid antibodies (APA) have acquired great relevance as atherogenic factors. Kidney graft recipients have a higher prevalence of cardiovascular disease (CVD) than the general population, which is not fully explained by the classical vascular risk factors. The aim of this study was to assess the influence of APA on kidney graft and patient outcomes with special focus on CVD. Materials and Methods: One hundred ninety seven cadaveric kidney graft recipients with functioning grafts for more than 1 year underwent determination of serum APA titres (anti-cardiolipin and anti-beta-2 glycoprotein I IgG and IgM antibodies) in one pretransplant serum and in second one obtained at least 1 year after transplantation. In the case of postransplant CVD, the postransplant serum was always chosen before the cardiovascular event. The enzyme linked immunosorbent assay (ELISA) for anti-cardiolipin antibodies was performed in the presence of cofactor. Results: Twenty-seven percent of patients had pretransplant APA, whereas 15.7% developed postransplant APA de novo. The presence of pretransplant serum APA was not associated with a higher risk of postransplant CVD. The development of postransplant APA de novo showed a relationship to an acute rejection episode (ARE): the frequency of patients who had APA de novo was higher among patients who suffered ARE (18.8% vs 7%, P = .01). In addition, in patients who suffered any ARE, the production of postransplant APA was associated with a higher frequency of postransplant CVD. Conclusions: The detection of APA is not an independent risk factor for CVD after kidney transplantation. The inflammatory phenomena secondary to an ARE may be responsible for the de novo production of postransplant APA, which may be associated with the development of postransplant CVD. The control of cardiovascular risk factors should be intensified in this special group of patients. [Copyright &y& Elsevier]

Abstract: Renal function within the first year after transplantation has been shown to be an important parameter influencing long-term survival. In this study, we examined the relationship between long-term outcome in 365 renal transplants and renal function in the first year, expressed as serum creatinine (SCr) level at 6 months and at 1 year as well as namely ¿Cr, the change in SCr between 6 months and 1 year. In addition, we examined the influence of the presence of proteinuria as a predictive factor for a worse evolution. Graft survival was worse among patients with higher ¿Cr, especially among those who developed proteinuria. In a Cox regression analysis of long-term graft survival, both ¿Cr and proteinuria were important predictors of half-life. The risk of graft loss when ¿Cr >0.3 was 2.65 (1.8¿3.8; P < .000), whereas the risk increased to 5.67 (3.3¿9.4; P < .00) when proteinuria was present. In conclusion, ¿Cr values predict long-term graft survival. Patients who developed proteinuria were at higher risk for graft loss compared with those without proteinuria. By using a combination of SCr and ¿Cr with proteinuria, it is possible to identify a subset of transplant recipients with a predictably shortened half-life. [Copyright &y& Elsevier]

Abstract: Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 ± 0.8 mg/dL, 1.8 ± 0.7 mg/dL, 1.5 ± 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis. [Copyright &y& Elsevier]

Elevated pulse pressure in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplant patients. We investigated the effects that a wide pulse pressure has on cardiovascular disease after renal transplantation in a cohort of 532 transplant patients with functioning grafts for more than one year. Patients were classified into two groups depending on whether the one-year pulse pressure was less than or greater than 65 mm Hg. We analyzed patient survival, posttransplant cardiovascular disease and principle causes of death. Five- and ten-year patient survival were lower among the group with higher pulse pressures. The main cause of death was vascular disease in both groups. The presence of posttransplant cardiovascular disease was higher among the group with higher pulse pressures (RR = 1.73). In addition, the incidence of an elevated pulse pressure was directly associated with recipient age and posttransplant diabetes mellitus. In conclusion, pulse pressure represents an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients. [Copyright &y& Elsevier]

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73m2). The GFR was estimated as the average Cr and urea clearances.The mean GFR estimated by averaged Cr and urea clearances (22.18 ± 5.23 mL/min per 1.73m2) was significantly different from the mean values yielded by the MDRD formula (20.42 ± 6.65 mL/min per 1.73m2, P = .000), the Nankivell formula (30.14 ± 11.98 mL/min per 1.73m2, P = .000), and the CG formula (29.42 ± 8.64 mL/min per 1.73m2, P = .000). The MDRD formula showed a better correlation (R = 0.741, P = .000) than the CG (R = 0.698, P = .000) and the Nankivell formulas (R = 0.685, P = .000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: −1.65 ± 4.4 mL/min per 1.73m2; CG: 7.33 ± 6.24 mL/min per 1.73m2; Nankivell: 8.05 ± 9.23 mL/min per 1.73m2) and narrower limits of agreement (Nankivell: −10.41–26.51 mL/min per 1.73m2; CG: − 5.15–19.81 mL/min per 1.73m2; MDRD: −10.61–7.31 mL/min per 1.73m2).In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR. [Copyright &y& Elsevier]