Patricia Delgado

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.

Renin–angiotensin system blockade and kidney transplantation: a longitudinal cohort study

BACKGROUND The beneficial effect of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in kidney transplant recipients on modern immunosuppression is not yet well established. Our objective was to investigate the impact of the use of ACEI/ARB on patient and graft survival in a cohort of kidney transplant recipients. METHODS A total of 990 patients, who received a single deceased donor kidney at our institution between 1996 and 2005, were included in this longitudinal cohort study. All-cause mortality and death-censored graft loss were the primary outcomes. We used traditional time-dependent Cox model (unweighted) and inverse-probability-of-treatment weighting of marginal structural models (weighted Cox model), controlling for time-dependent confounding by indication. RESULTS A total of 414 patients (42%) received ACEI/ARB through the study period (median duration 14 months, interquartile range 6-40 months). ACEI/ARB use was associated with reduction of risk for mortality in the crude [hazard ratio (HR) 0.627, 95% confidence interval (CI) 0.412-0.953] and adjusted Cox analysis (HR 0.626, 95% CI 0.407-0.963). Similar results were observed after adjusting for confounding by indication (HR 0.629, 95% CI 0.407-0.973). By contrast, ACEI/ARB use was not associated with significant improvement of graft survival after kidney transplantation. CONCLUSION ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.

Metabolic syndrome, insulin resistance, and chronic allograft dysfunction.

Metabolic syndrome (MS) is a cluster of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and glucose homeostasis alterations), and insulin resistance (IR) is suggested to be a common pathogenic background. In the general population, MS and IR have been proven to be risk factors for diabetes, CV disease, and chronic kidney disease. In the renal transplant setting, few studies have analyzed the relevance of MS and IR. According to the few data available, the prevalence of MS in renal transplant patients has been described as 22.6% at 12 months, 37.7% at 36 months, and 64% at 6 years after transplantation. Importantly, MS has been shown to be an independent risk factor for chronic allograft dysfunction (CAD), graft failure, new-onset diabetes, and CV disease. Also, persistent hyperinsulinemia during the first posttransplant year has been related to an increase in glomerular filtration rate, probably reflecting glomerular hyperfiltration as observed in prediabetes and early type 2 diabetes. Importantly, prediabetes (impaired fasting glucose and impaired glucose tolerance), a state hallmarked by IR, proved to be highly frequent among stable renal transplant recipients (30%), which is nearly three times its incidence in the general population. Posttransplant IR has been associated with subclinical atheromatosis as assessed by carotid intima-media thickness, and with chronic subclinical inflammation. In conclusion, MS and IR are important modifiable risk factors in renal transplant recipients, and prompt interventions to avoid its deleterious effects at the metabolic, CV, and graft function levels are needed.

Early association of low-grade albuminuria and allograft dysfunction predicts renal transplant outcomes.

Background. Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction. Methods. We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0–470 mg/day) and median eGFR (60 mL/min/1.73 m2; interquartile range, 30–73 mL/min/1.73 m2) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria ≥100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR ⩽60; n=167); and group IV (albuminuria ≥100 and eGFR ⩽60, n=228). Results. Death-censored graft survival was significantly lower in group IV compared with the rest (P<0.0001). Multivariate Cox regression analysis using fixed and time-dependent covariates showed that the combination of low-grade albuminuria and lower eGFR was associated with graft failure (hazard ratio, 2.2, 95% confidence interval, 1.3–3.7; P=0.003). Likewise, but to a lesser extent, the risk of mortality was increased for group IV (hazard ratio, 1.7, 95% confidence interval, 1.01–2.8; P=0.042). Conclusions. Early association of low-grade albuminuria and allograft dysfunction represents an important risk factor of graft failure and mortality. This additive effect should be considered to identify individuals at risk for adverse kidney transplantation outcomes.

Impact of cold ischemia time on renal allograft outcome using kidneys from young donors

Prolonged cold ischemia time (CIT) is associated with delayed graft function and worse kidney transplant (KT) outcome, but the effect of CIT on long‐term allograft survival in KT from younger donors has not been well established. We investigated the predictive value of CIT exposure on long‐term death‐censored graft loss in 829 KT recipients from younger donors (<50 years) that were performed in our center between 1991 and 2005. Overall death‐censored graft failure rate was significantly higher in CIT≥19 h group versus CIT<19 h group (26 vs. 16.5%; P = 0.002). Significant differences were also observed when patients with primary nonfunctioning graft were excluded (21 vs. 14%; P = 0.020) and in patients who received tacrolimus plus mycophenolate mofetil (12 vs. 4%; P = 0.05). By multivariate Cox analysis, CIT was found to be independently associated with death‐censored graft loss with a 20% increase for every 5 h of CIT [relative risk (RR) 1.04; 95% Confidence Interval (CI): 1.01–1.1; P = 0.021]. Likewise, graft loss risk significantly increased in CIT≥19 h group versus CIT<19 h group (RR 1.5; 95%CI: 1.1–2.1; P = 0.023). Prolonged CIT is an independent predictor of graft survival in KT from younger donors. Efforts at minimizing CIT (<19 h) should improve transplant outcome significantly in this population.

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.

Carotid atheromatosis in nondiabetic renal transplant recipients: the role of prediabetic glucose homeostasis alterations.

Background. Prediabetic glucose homeostasis alterations are important cardiovascular risk factors but their role in renal transplant recipients (RTR) has not been established. Methods. In 172 RTRs without pretransplant or de novo diabetes, we measured carotid intima media thickness (c-IMT) and performed an oral glucose tolerance test (OGTT). Results. In multivariate analysis, age, hypertension and male sex were independently associated with a c-IMT in the third tertile. A significant interaction between gender and glucose homeostasis parameters was observed. Among male RTR, those with a c-IMT in the third tertile showed significantly higher plasma glucose and HbA1c levels (5±0.5% vs. 5.1±0.5% vs. 5.5±0.4%; P<0.01 tertile 3 vs. 2 or 1) than those in other tertiles. Insulin action parameters were not significantly different. The odds ratio of being in the higher c-IMT tertile was 2.9 (95% CI: 1.05–8.1) per each 1% increase of HbA1c. By contrast, glucose and HbA1c levels were not significantly different between c-IMT tertiles in female RTR. However, age-adjusted insulin levels after OGTT were higher (86±10 vs. 51.7±9.4; P=0.02) and the insulin sensitivity index lower (0.8±0.3 vs. 0.048±0.03; P=0.04) among females in the third tertile as compared to the first one. Conclusion. Prediabetic glucose homeostasis alterations in RTRs are related to carotid atherosclerosis, although there may be gender differences in the underlying alteration.

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 &mgr;U/mL; 12 months: 8.74 &mgr;U/mL) at both periods. The 3 to 12 months percent change in calculated creatinine clearance (3–12 months &Dgr;CrCL) was calculated. Results. Patients with persistent hyperinsulinemia showed a higher increase in 3 to 12 months &Dgr;CrCL compared with those with persistent normoinsulinemia (12% [−20/40] vs. −0.03% [−12/18], P=0.035). We performed a multivariate linear regression analysis with the 3 to 12 months &Dgr;CrCL as the dependent variable and different factors that may induce hyperfiltration, including persistent hyperinsulinemia, as covariates. Persistent hyperinsulinemia was a risk factor for increased CrCL (&bgr; 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.

Síndrome de Goodpasture asociado con vasculitis cerebral ANCA negativa

Goodpastures syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.