Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant.

BACKGROUND: Advanced glycation end products (AGEs) accumulation, a measure of cumulative metabolic stress, constitute a novel pathogenic mechanism involved in aging, diabetes, cardiovascular (CVD) and chronic kidney disease (CKD). Despite removal of uremic toxins and AGEs after a successful renal transplant (RT), CVD remains the leading cause of mortality. We hypothesized that AGEs measurement by Skin Autofluorescence (SAF) might be useful even after a successful RT and thus reflect the high cardiovascular risk burden of these patients. METHODS: 189 stable RT (61% men, aged 56±13.0 years), CKD stages 1-4 and >12 months since RT were enrolled. Variables collected comprised comorbid history, medication use, smoking habit, routine biochemistry, subclinical atheromatosis by ankle-brachial-index (ABI) and allograft resistivity index (RI), 24-h ABPM, anthropometry and handgrip strength. AGEs were measured by SAF and expressed in arbitrary units (AU). Vascular age was estimated by Koetsier´s formula (SAF-0.83/0.024) and expected 10-years cardiovascular death risk was calculated with the REGICOR score. RESULTS: Mean SAF was 3.00±0.83 AU and estimated vascular age 90±34.7 years (30 years above biological age). SAF was higher among men (3.10±0.91 vs 2.81±0.66), diabetic nephropathy (3.49±0.75 vs 2.96±0.83) and steroid users (3.14±0.86 vs 2.71±0.69). We observed a positive correlation of SAF with night-systolic blood pressure (r = 0.25, p = 0.001), parathormone (r = 0.20, p<0.01), phosphate (r = 0.28, p<0.001) and negative with hemoglobin (r = -0.29, p<0.001), CKD-EPI (r = -0.32, p<0.001), albumin (r = -0.17, p<0.05), and dynamometry (r = -0.20, p<0.01). Subclinical vascular atheromatosis (ABI and RI) as well as the REGICOR scale (r = 0.35 p<0.001) were also correlated with SAF. In multivariable analysis age, gender, steroid use, serum phosphate and handgrip strength remained independently associated with SAF. CONCLUSIONS: SAF levels are elevated in RT patients and correlate with CVD risk. Besides age and male sex, our results suggest that phosphate overload, steroid use and nutritional status are important factors linking to AGEs accumulation.

Comprehensive Approach to Peritoneal Dialysis-Related Peritonitis by Enteric Microorganisms. Comparison Between Single Organism and Polymicrobial Infections.

BACKGROUND: Peritoneal infections of enteric origin (EntP) have been classically investigated using partial strategies, focused on particular subgroups of microorganisms. A more comprehensive approach may facilitate the definition of the nomenclature and clinical presentation of these infections. OBJECTIVES: To investigate the clinical presentation and outcomes of a full spectrum of EntP, with a particular interest in the comparison between single-organism and polymicrobial infections. METHOD: Following an observational design, we investigated 165 single-organism and 83 polymicrobial peritonitis episodes with isolation of at least 1 enteric bacteria (Enterobacteriaceae, Enterococcus spp. and/or intestinal anaerobics). We compared the risk of treatment failure for these 2 types of infection and explored the significance of the isolation of specific microorganisms and of their antibacterial susceptibility patterns. RESULTS: Polymicrobial EntP was associated with higher rates of hospitalization, more changes to initial antibiotic therapy, more surgical explorations, and higher mortality and treatment failure rates than monobacterial EntP. However, stratified and multivariate analyses revealed that the burden of these differences rested on the isolation of intestinal anaerobics (odds ratio [OR] 12.05, 95% confidence interval [CI] 2.53-31.09, p < 0.001) and/or Enterococcus faecium (OR 3.37, 95% CI 1.02-11.30, p = 0.046), while other polymicrobial infections were more comparable with single-organism peritonitis, except for even higher mortality rates in the former group. Lower antibiotic susceptibility of the isolations (OR 1.18, 95% CI 0.51-2.70, p = 0.70) did not perform as a predictor of treatment failure. CONCLUSION: A comprehensive approach to peritoneal infections by intestinal microorganisms may provide a focused perspective of the clinical presentation and outcomes of these complications of peritoneal dialysis.

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis.

BACKGROUND: Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). METHOD: Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. MAIN RESULTS: The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08-2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. CONCLUSIONS: Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients.