Standardizing health outcomes for chronic kidney disease. Adaptation of the international consortium for health outcomes measurement standard set to the Spanish setting.

BACKGROUND AND OBJECTIVES: We aim to adapt the International Consortium for Health Outcomes Measurements standard set for chronic kidney disease (CKD) patients to the Spanish setting and supplement it with those variables agreed upon through initiatives proposed by the Spanish Society of Nephrologists (S.E.N.). MATERIAL AND METHODS: The working group defined a first standard set of variables based on a literature review. The S.E.N. members then assessed the suitability of each variable for inclusion (Consensus≥75%). A second draft of the standard set was generated and evaluated by the Patient advocacy group Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER). Lastly, the working group established the final standard set of variables (Consensus≥75%). RESULTS: The standard set targets patients with very high-risk CKD (G3a/A3 and G3b/A2-G5) in pre-end-stage kidney disease (pre-ESKD), hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT) or conservative care (CC). The essential follow-up variables agreed for all patients (All) were patient survival, hospitalizations, cardiovascular events, smoking status, health-related quality of life, pain, fatigue, physical function, daily activities, depression, renal function and hemoglobin. Additionally, it was agreed to collect PD survival (in PD patients), peritonitis (PD), infection/bacteremia (PD, HD, KT), vascular access type (HD), vascular access survival (HD), acute rejection (KT), post-transplant cancer (KT), albuminuria (KT) and kidney allograft survival (KT). The optional variables agreed were phosphorus (All), potassium (All), diabetes control (All with diabetes), and albuminuria (pre-ESKD). CONCLUSIONS: This standard set may constitute a highly efficient tool allowing the evaluation of patient outcomes and helping to define strategies to enhance CKD patients' quality of care in the Spanish healthcare system.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

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 (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥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 100pg/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.

Metabolic syndrome in hemodialysis patients as a risk factor for new-onset diabetes mellitus after renal transplant: a prospective observational study.

PURPOSE: 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.

Uromodulin and α(1)-antitrypsin urinary peptide analysis to differentiate glomerular kidney diseases.

BACKGROUND/AIMS: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. METHODS: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. RESULTS: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α(1)-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80-92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels - focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. CONCLUSION: We describe a workflow - urinary peptide profiling coupled with histological findings - that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

UNLABELLED: 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<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >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.

Proteomic approach to the study of statin pleiotropy in kidney transplant patients.

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.

Validation of estimated renal function measurements compared with the isotopic glomerular filtration rate in an HIV-infected cohort.

We performed a cross-sectional study to determine the best method for estimating the glomerular filtration rate (GFR) in HIV-infected subjects. Isotopic GFR was correlated with 24-h urine creatinine clearance, cystatin C levels, and 3 creatinine-based equations-the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-in 15 patients. Cystatin C showed the strongest correlation with isotopic GFR (r=-0.760, p=0.001). When cystatin C was used as the reference variable for all 106 patients, CKD-EPI proved to be superior to the other equations (r=-0.671, p<0.001). Time with HIV infection, unsuppressed viral load, low CD4 T-cell counts, and use of protease inhibitors are related to an increased risk of renal impairment, leading us to recommend early initiation of antiretroviral therapy accompanied by a regular renal study.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in renal transplantation between 1990 and 2002 in Spain.

Background. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) decrease cardiovascular mortality and slow the progression of renal disease in non-transplant patients, but their impact on kidney transplant outcome has not been well established.Methods. Patients receiving a renal allograft in Spain in 1990, 1994, 1998 and 2002 were considered for the present study. Only adult (>/=18 years) recipients of a single kidney transplant functioning at the end of the first year were considered. A total of 4842 patients with clinical data about ACEI/ARB therapy were included.Results. During the initial 2 years after transplant, ACEI/ARB were less frequently used in the 1990 and 1994 cohorts than in 1998 and 2002 (15.1%, 24.6%, 33.5% and 45.1%, respectively; P < 0.001). During the first year, a total of 1063 patients (22.8%) received ACEI/ARB treatment, and graft survival (50.0% for treated patients and 51.4% for untreated, P = ns), death-censored graft survival (60.6% versus 63.5%, P = ns) and patient survival (68.8% versus 66.6%, P = ns) were not different. During the initial 2 years, 1472 patients (31.4%) received treatment with ACEI/ARB, and graft survival tended to be higher in treated patients (54.4% and 50.9%, P = 0.063). Since there was an interaction between ACEI/ARB treatment and year of transplant, graft survival was analysed in each cohort. Cox regression analysis including the propensity score for ACEI/ARB treatment showed an association between ACEI/ARB treatment and graft survival in the 2002 cohort (relative risk 0.36 and 95% confidence interval 0.17-0.75, P = 0.007). Death-censored graft survival (63.8% versus 63.1%, P = ns) and patient survival (68.1% and 66.5%, P = ns) were not significantly different.Conclusions. The use of ACEI/ARB during the initial 2 years after transplantation was associated with a better graft survival, but this effect was only observed in the 2002 cohort.

Hyperinsulinemia and hyperfiltration in renal transplantation.

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 muU/mL; 12 months: 8.74 muU/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3-12 months DeltaCrCL) was calculated. RESULTS: Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months DeltaCrCL 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 DeltaCrCL 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.

Obesity, inflammation, and kidney disease.

Obesity and extreme obesity are associated with a wide range of well known comorbidities (cardiovascular disease, dyslipidemia, hypertension, diabetes mellitus, metabolic syndrome). Recently, the association between obesity and renal involvement has been accepted since several epidemiological and pathological studies support this relationship. However, the physiopathological mechanism of this association is not completely understood. Different mechanisms have been implicated in the production of these renal lesions. Between them, metabolic alterations and inflammatory adipocytokines have been suggested. This paper is a review of the association between inflammatory adipocytokines or metabolic syndrome with renal involvement. We also briefly report our experience in a cohort of extremely obese patients.

Pretransplant inflammation: a risk factor for delayed graft function?

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Pretransplant inflammation (TNF-alpha, PAPP-A) in transplant recipients could be a risk factor for the development of DGF.

Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study.

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.

Unmasking glucose metabolism alterations in stable renal transplant recipients: a multicenter study.

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 beta 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.

Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients?

BACKGROUND: The aim of this study was to compare the accuracy of prediction equations [modification of diet in renal disease (MDRD), simplified MDRD, Cockcroft-Gault (CG), reciprocal of creatinine and creatinine clearance] in a cohort of patients with type 2 diabetes. METHODS: A total of 525 glomerular filtration rates (GFRs) using (125)I-iothalamate were carried out over 10 years in 87 type 2 diabetic patients. Accuracy was evaluated at three levels of renal function according to the baseline values obtained with the isotopic method: hyperfiltration (GFR: >140 ml/min/1.73 m(2); 140 isotopic determinations in 27 patients), normal renal function (GFR: 140-90 ml/min/1.73 m(2); 294 isotopic determinations in 47 patients) and chronic kidney disease (CKD) stages 2-3 (GFR: 30-89 ml/min/1.73 m(2); 87 isotopic determinations in 13 patients). The annual slope for GFR (change in GFR expressed as ml/min/year) was considered to ascertain the variability in the equations compared with the isotopic method during follow-up. Student's t-test was used to determine the existence of significant differences between prediction equations and the isotopic method (P < 0.05 with Bonferroni adjusted for five contrast tests). RESULTS: In the subgroup of patients with hyperfiltration, a GFR slope calculated with (125)I-iothalamate -4.8 +/- 4.7 ml/min/year was obtained. GFR slope in patients with normal renal function was -3.0 +/- 2.3 ml/min/year. In both situations, all equations presented a significant underestimation compared with the isotopic GFR (P < 0.01; P < 0.05). In the subgroup of CKD stages 2-3, the slope for GFR with (125)I-iothalamate was -1.4 +/- 1.8 ml/min/year. The best prediction equation compared with the isotopic method proved to be MDRD with a slope for GFR of -1.4 +/- 1.3 ml/min/year (P: NS) compared with the CG formula -1.0 +/- 0.9 ml/min/year (P: NS). Creatinine clearance presented the greatest variability in estimation (P < 0.001). CONCLUSIONS: In the normal renal function and hyperfiltration groups, none of the prediction equations demonstrated acceptable accuracy owing to excessive underestimation of renal function. In CKD stages 2-3, with mean serum creatinine > or =133 micromol/l (1.5 mg/dl), the MDRD equation can be used to estimate GFR during the monitoring and follow-up of patients with type 2 diabetes receiving insulin, anti-diabetic drugs or both.

Oxidative stress, inflammation and cardiovascular mortality in haemodialysis--role of seniority and intravenous ferrotherapy: analysis at 4 years of follow-up.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality in haemodialysis patients. The classic risk factors do not account for all cases of elevated cardiovascular disease in this patient population and it is becoming increasingly clear that other cardiovascular risk factors are implicated. The objective of this study was to analyse whether or not C-reactive protein (CRP) and plasma copper oxidized anti-lipoprotein (oxLDL) antibody titre are risk factors for cardiovascular mortality during 4 years of follow-up. METHODS: A prospective follow-up study was carried out in 94 stable, chronic haemodialysis patients for 48 months (July 1999-July 2003) (gender: 50 males and 44 females; mean age: 67+/-14 years). Eighty-four per cent of these patients were receiving intravenous erythropoietin and 63% were receiving intravenous ferrotherapy (iron gluconate). Basal markers of inflammation and oxidative stress were determined at the beginning of the study. CRP levels were determined by chemiluminescent enzyme-labelled immunometric assay. The oxLDL antibody titre was measured by enzyme-linked immunosorbent assay using native LDL and oxLDL as antigens. RESULTS: Fifty deaths occurred during the study, 66% (n = 33) of which were due to cardiovascular disease. Patients presented with basal CRP and oxLDL levels indicative of chronic inflammation and elevated oxidative stress [CRP median: 5.16 mg/l (25-75% percentile: 0.35-88.7 mg/l); oxLDL antibodies median: 153 (optical density at 495 nm x 1000) (25-75% percentile: 112-214)]. A positive correlation was found between CRP and age (r = 0.33, P = 0.003). Study of the risk factors demonstrated that age (P = 0.007), oxLDL antibody titre (P = 0.04) and albumin (P = 0.02) were the only predictors of cardiovascular mortality at 4 years of follow-up in this patient population. The Cox proportional hazards model for cardiovascular mortality showed that of the markers studied, oxLDL antibody titre was an independent risk factor for cardiovascular mortality. CONCLUSIONS: Oxidative stress (oxLDL antibody titre) is one of the principal risk factors for cardiovascular mortality in this population of haemodialysis patients. Intravenous ferrotherapy, due to its pro-oxidant properties, probably favours oxidative stress. Serum concentration of CRP was not a good predictive factor of cardiovascular mortality during 4 years of follow-up, possibly because of the slight positive correlation that exists between CRP and age.

Pretransplant pregnancy-associated plasma protein-a as a predictor of chronic allograft nephropathy and posttransplant cardiovascular events.

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<0.001; PAPP-A vs. TNF-alpha, r=0.372; P<0.001). The multiple regression analysis showed PAPP-A (relative risk [RR]: 6.4; 95% confidence interval [CI]:1.24-33.11; P=0.027) and CRP (RR: 6.05; 95% CI:1.21-29.74; P=0.028) to be predictors of posttransplant cardiovascular events and PAPP-A (RR: 4.27; 95% CI: 1.03-17.60; P=0.044) and TNF-alpha (RR: 5.6; 95% CI: 1.43-21.83; P=0.013) to be predictors of CAN. CONCLUSIONS: PAPP-A correlated with the inflammatory markers studied (CRP, IL-6 and TNF-alpha). Pretransplant serum concentration of PAPP-A is a predictor of posttransplant cardiovascular events and CAN.

"New" cardiovascular risk factors in patients with chronic kidney disease: role of folic acid treatment.

Cardiovascular disease (CVD) is the principal cause of mortality in patients with chronic renal disease undergoing hemodialysis. In addition to the CVD risk factors, a new hypothesis has recently been aroused related to "new" factors involved in the development of atherosclerosis in the uremic patient; worthwhile mentioning are the homocysteine, inflammation, and oxidative stress, among others. The potential utility of the folic acid in the hyperhomocysteinemia control is well known, although its mechanism of action, either as antioxidant or anti-inflammatory, has not been established. Our results confirm that the patients undergoing dialysis demonstrate hyperhomocysteinemia, an increased inflammatory status, and an increase of the lipid peroxidation markers. The administration of IV folinic acid induces a reduction of homocysteine levels subordinate to the inflammatory status of the patient. Additionally, although no inflammatory effects were shown, the results provide evidence for the antioxidant effect of IV folinic acid administration by reducing the lipid peroxidation marker levels. The statistic analysis demonstrates no correlation among the 3 markers, in spite of its higher levels in these particular patients. Homocysteine does not independently predict mortality in patients taking oral folic acid. Nevertheless, the PCR (an inflammation marker) and the antibody antioxidative-LDL (a lipidic peroxidation marker) show a good prediction of mortality at the 24-month follow-up analysis. The knowledge of these "new" CV risk factors, as well as the factors that influence them, could be useful to prevent the development of atherosclerosis in patients with chronic renal disease.