Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Prognostic Value of Modified Banff Score in the Evolution of Renal Function.

BACKGROUND: Some lesions not included in the Banff classification, such as inflammation in the scarred areas and total inflammation, have been described to have prognostic value in the evaluation of graft biopsies. Our aim was to reassess kidney graft biopsies and study the impact of histopathologic lesions, both those graded in the Banff classification and those related to inflammation, on the graft function and evolution. METHODS: We selected 20 biopsies exhibiting chronic pathology without a specific phenotype, and we reevaluated them with the use of a modified Banff score. RESULTS: We found statistically significant association between the presence of total inflammation (P = .048; P = .038), the presence of inflammation in scared area (P = .037; P = .018), and creatinine at the time of renal biopsy and 1 year after the renal biopsy, respectively. CONCLUSIONS: Our results suggest that the presence of both inflammation in the scarred areas and total inflammation are related to renal function at the time of the biopsy and to renal function 1 year after the biopsy.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Outcomes of Monoclonal Gammopathy of Undetermined Significance in Patients Who Underwent Kidney Transplantation.

BACKGROUND: There are few reports about the clinical course and prognosis of monoclonal gammopathy of undetermined significance (MGUS) in long-term immunosuppressed patients. Our aim was to study the association and evolution of MGUS and renal transplantation. METHODS: Subjects submitted to renal transplantation between 1996 and 2011 who presented MGUS before or after immunosuppressive treatment was established were selected. RESULTS: Patients (N = 587) underwent kidney transplantation in our center during the selected period. MGUS was detected in 17 (2.9%) patients (10 men and 7 women with a mean age of 69.9 ± 10.07 years), with a median follow-up of 6 years. All patients had a functioning graft. Nine had MGUS before transplantation. One patient had multiple myeloma, and 8 remained stable. Eight patients had development of MGUS after transplantation. Six patients remained stable, 1 showed no MGUS, and 1 displayed an increased monoclonal component in further controls. CONCLUSIONS: In our study, renal transplantation is not a risk factor for the development of malignant processes in patients with MGUS before transplantation. There is a group of patients who tend to have MGUS after transplantation; nevertheless, they had a benign evolution during a 6-year follow-up.

Recurrent Glomerulonephritis in Renal Transplantation: Experience in Our Renal Transplantation Center.

BACKGROUND: Post-transplant recurrent glomerulonephritis (RGN) is the third cause of graft failure in the first year after renal transplantation (RT). The purpose of this study was to analyze the incidence of RGN, clinical presentation, and clinical evolution of transplanted renal graft in patients who underwent RT at our center. METHODS: We studied patients with glomerulonephritis (GN) who underwent RT (2007 to 2013).We analyzed sex, age, time in dialysis, type of GN, type of RT, time to post-transplant RGN, kidney function at the time of diagnosis of RGN, and renal graft evolution. Renal biopsy samples were processed in the anatomic pathology laboratory. RESULTS: Three hundred sixteen patients received kidney transplantation during this time period. In 83 cases, the reason for transplantation was primary GN. Of these 83 patients, 15 (18%) had RGN confirmed by renal biopsy. Data for these 15 patients include sex: 73.3% men, 26.7% women; mean age: 42.2 (29-73) years; type of RT: 80% cadaveric donor (CD) versus 20% living donor (LD); type of GN: 18.4% immunoglobulin (Ig)A nephropathy, 35.7% membranous GN, 10.53% type I membrano-proliferative GN (MPGN I), and 16.6% focal segmental glomerular sclerosis (FSGS). The mean time to post-transplant RGN was 2 years (1 month to 16 years). Patients who received an LD transplant had a shorter time to post-transplant RGN than those who had a CD transplant. One patient with FSGS and one with MPGN I had a time to post-transplant RGN of less than 1 year. In the evolution of renal function, 33.3% of patients had graft failure. CONCLUSIONS: The incidence of RGN was lower (18%) than that published in the literature. Membranous nephropathy was the most frequent cause of post-transplant RGN. Patients who underwent LD transplantation and those with IgA nephropathy had a shorter interval of time to post-transplant RGN than patients with FSGS and MPGN I.

Late Onset of Cholesterol Embolism Leading to Graft Failure After Renal Transplantation: Report of Two Cases.

Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.

Nodular Arteriolar Hyalinosis as Histopathologic Hallmark of Calcineurin Inhibitor Nephrotoxicity: Does It Always Have the Same Meaning?

INTRODUCTION: Nodular arteriolar hyalinosis (NAH) is a typical, although not specific, histological finding of calcineurin inhibitor toxicity (CNIT). The objective of our study was to assess the reason why some patients showing strong NAH in renal graft biopsies who underwent calcineurin inhibitor (CNI) withdrawal presented very poor outcome whereas others improved graft function. MATERIAL AND METHODS: We performed 207 renal graft biopsies between January 2011 and May 2014 due to clinical criteria. In 13 patients CNI withdrawal was performed, and the major histopathological finding was severe NAH. The results after this action were analyzed. RESULTS: We selected 2 groups: good outcome and poor outcome. Eight patients showed good results including stabilization or improvement of graft function. Five patients presented poor results requiring chronic hemodialysis. C4d staining was negative in all biopsy specimens, and peritubular capillaritis was not observed. To identify potential prognostic markers we retrospectively reviewed biopsy samples looking for minor or nonspecific features, especially inflammation scores both global and on fibrotic areas as per Banff classification. Mean serum creatinine level at time of biopsy and mean arteriolar hyalinosis score did not show significant differences between both groups. In contrast, the poor results group presented a higher mean global inflammation score compared with the good results patients. CONCLUSIONS: NAH is not a risk factor for poor renal graft outcome by itself. Other histopathologic findings, usually considered as secondary markers, like the inflammation score, should be considered before deciding CNI withdrawal.

Evaluating the impact of gastrointestinal episodes on the health-related quality of life of solid organ transplant recipients: sensitivity to change of the SIGIT-QoL questionnaire: Mypaciente-2 study.

A significant proportion of transplant patients undergoing immunosuppressant therapy experience gastrointestinal (GI) symptoms. The SIGIT-QoL is a brief instrument developed to measure adverse gastrointestinal effects on patients' health-related quality of life (HRQoL). The goal of this study was to analyze the psychometric properties of the SIGIT-QoL that are required for its use in clinical research and practice, especially its value for detecting changes in the impact of gastrointestinal symptoms on HRQoL of solid organ transplant (SOT) recipients. To this end, an observational, multicenter, prospective study was conducted. SOT patients aged ≥18 years who had received the graft 3 to 24 months before and were experiencing gastrointestinal symptoms were evaluated at baseline, 1 to 2 weeks later, and 3 months after baseline. Sociodemographic and clinical data recorded included: age, sex, SOT type (lung, kidney, liver, or heart), acute allograft rejection, gastrointestinal etiology, Clinical Global Impressions (CGI) and Patient Global Impression (PGI) Severity of Illness (SI) and Global Improvement (GI) scores, and the SIGIT-QoL (scores range from 0 [maximum impact] to 68 [minimum disruption]). Intraclass correlation coefficients, differences between baseline and last visit (Wilcoxon test), effect size (Cohen's d), the minimal important differences (using CGI and PGI scores as anchors in General Linear Models), and the cutoff score (receiver-operating characteristic analysis) were calculated. In total, 277 SOT patients (61.4% male) were included. Mean ± SD age was 52.69 ± 11.65 years, time since transplantation was 12.31 ± 6.74 months, and 22.4% experienced an acute allograft rejection. At baseline, total SIGIT-QoL mean scores (51.21 ± 11.25) showed an impact on patients' HRQoL that was diminished 3 months later (57.40 ± 8.38; P < .001). SIGIT-QoL test-retest reliability was adequate (intraclass correlation coefficient, 0.740-0.895). A moderate effect size (d = -0.550) was found. Moreover, a minimal important difference of 4.2 points in total scores was found (F4,223 = 16.917 [P < .001] and F4,224 = 25.138 [P < .001]). Finally, a cutoff point (55.00 points) was estimated (area under the concentration-time curve, 0.846 [95% confidence interval, 0.798-0.894], P < .001; sensitivity, 0.793; specificity, 0.713; negative likelihood ratio, 0.290; positive likelihood ratio, 2.762). We concluded that the SIGIT-QoL is a feasible (average completion time, <6.5 minutes), reliable, and valid instrument for assessing the impact of gastrointestinal symptoms on the HRQoL of SOT patients.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Posttransplantation anemia: relationship with inflammatory markers, oxidation, and prohepcidin levels.

BACKGROUND: Anemia frequently occurs after kidney transplantation, its origin is multifactorial. The objective of this study was to evaluate the frequency of anemia among kidney transplantation patients at 3 months after transplantation and its relationship to inflammatory, oxidative, and nutritional states. Furthermore, we determined serum prohepcidin, a precursor of hepcidin, the main hormone implicated in iron metabolism. MATERIALS AND METHODS: We performed a transverse retrospective study in 130 patients who underwent kidney transplantation, including 89 men and 41 women. Patients were randomized according to the presence or absence of anemia at 3 months. The patients' inflammatory, oxidative, and nutritional states were evaluated as well as renal function and serum prohepcidin at 3 months. RESULTS: Twenty-four percent of the patients developed anemia at 3 months after transplantation. These patients presented with a greater inflammatory state, a poor nutritional status, and poor renal function. Serum prohepcidin was significantly lower compared with the transplantation patients who did not show anemia. CONCLUSIONS: Serum prohepcidin was significantly higher among kidney transplantation patients who did not develop anemia. The inflammatory state may be a determinant of the response to treatment with erythropoiesis-stimulating agents in anemic kidney transplant recipients.

Efficacy and safety of conversion from twice-daily to once-daily tacrolimus in a large cohort of stable kidney transplant recipients.

Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (± SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

Posttransplant inflammation associated with onset of chronic kidney disease.

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.

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.

Effect of paricalcitol on the urinary peptidome of kidney transplant patients.

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.

Hepcidin and iron deficiency in pre-kidney transplant 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 concentrations < 100 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 ferritin > 800 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: ferritin > 100 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%.

Effect of low doses of atorvastatin on the urinary peptide profile of kidney transplant patients.

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.

Perceived state of health is worse in kidney recipients younger than 60 years vs older than 60 years.

OBJECTIVE: To evaluate the differences in perceived state of health (PSH) according to patient age younger or older than 60 years. PATIENTS AND METHODS: One hundred sixty-two patients were entered on the waiting list for renal transplantation from July 2003 at 4 hospitals in California and were observed prospectively for 2 years. Data were obtained at baseline and at 3 and 12 months after transplantation. All patients answered a generic Perceived State of Health (PSH) questionnaire, the 36-item Short-Form Health Survey (SF-36), and the EuroQol (EQ-5D) questionnaire. Data were analyzed using the t test for independent variables and the chi(2) test for contingency tables. RESULTS: Patients aged 60 years or older had higher PSH scores compared with those younger than 60 years on all dimensions of the SF-36 and on the 2 summary scores. Scores for the physical domains were significantly improved at all follow-up visits. After transplantation, scores for the EQ-5D were higher for older patients vs younger patients (mean [SD], 80 [16] vs 67 [14]; P = .01). The PSH score for the older patients was similar to that for the general population (>45 points). The PSH scores for the physical and mental health domains were worse for the younger patients compared with the general population; no differences were noted for clinical variables. CONCLUSION: Patients older than 60 years have higher PSH scores compared with patients younger than 60 years. However, scores for the younger patients were significantly improved at 1 year after transplantation.

Greater posttransplant inflammation and oxidation are associated with worsening kidney function in patients with pretransplant diabetes mellitus.

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 (TNFalpha), soluble TNFalpha receptor (sTNFalpha-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: TNFalpha: r = -.235 (P = .012); sIL-2R: r = .441 (P < .001); and sTNFalpha-R: 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.

Diabetes mellitus postrasplante según técnica de diálisis previa al trasplante / No disponible

La diabetes mellitus postrasplante (DMPT) es una de las complicaciones más importantes del paciente trasplantado renal, pues tiene importantes repercusiones sobre la supervivencia del injerto y del paciente. El diagnóstico de DMPT debe realizarse según los criterios de la American Diabetic Association. Estudios recientes demuestran la utilidad de realizar un test de tolerancia oral a la glucosa a todos los pacientes. Son muchos los factores de riesgo que favorecen la DMPT. Controlando los factores modificables (inmunosupresión, obesidad, infecciones…) se puede reducirla incidencia de DMPT. Según los datos del RMRC los pacientes en diálisis peritoneal son más jóvenes, pero presentan un mayor porcentaje de dislipemia y obesidad. Datos recientes sugieren que la inflamación subclínica, la adiponectina y la ghrelina pueden ser un importante factor patogénico en el desarrollo de la resistencia a la insulina y la diabetes mellitus. No existen evidencias claras de que la técnica de diálisis influya en el estado inflamatorio subclínico y las adipocitoquinas. Según datos del grupo español de estudio de la DMPT existe relación entre las concentraciones de ghrelina y el sexo en los pacientes de diálisis peritoneal. La complicación metabólica más frecuente de los pacientes en diálisis peritoneal es la hiperglicemia. La hiperglicemia pretrasplante favorece la aparición de DMPT. No existen evidencias claras en la literatura que demuestren que la técnica de diálisis sea un factor de riesgo para la aparición de DMPT. Son necesarios más estudios multicéntricos que analicen las características clínicas y biológicas del paciente renal y su relación con la DMPT (AU)

Post-transplant diabetes mellitus (PTDM) is one of the most important complications in kidney transplant patients because it has a significant impact on graft and patient survival. Diagnosis of PTDM should be based on the American Diabetic Association criteria. Recent studies show the value of performing an oral glucose tolerance test in all patients. Multiple risk factors promote PTDM. PTDM incidence may be reduced by controlling modifiable factors (immune suppression, obesity, infections…). According to RMRC data, patients on peritoneal dialysis are younger, but have a greater incidence rate of dyslipidemia and obesity. Recent data suggest that subclinical information, adiponectin, and ghrelin may be a significant pathogenetic factor in development of insulin resistance and diabetes mellitus. There is no clear evidence that the dialysis procedure influences the subclinical inflammatory state and adipocytokines. According to data from the Spanish group for the study of PTDM, a relationship exists between ghrelin levels and sex in patients on peritoneal dialysis. The most common metabolic complication in patients on peritoneal dialysis is hyperglycemia. Pre-transplant hyperglycemia promotes the occurrence of PTDM. There is no clear evidence in the literature showing that the dialysis procedure is a risk factor for the occurrence of PTDM. Additional multicenter studies are required to analyze the clinical and biological characteristics of renal patients and their relationship to PTDM (AU)