Octogenarians with chronic kidney disease in the nephrology clinic: Progressors vs. non-progressors.

Background: The current definition of chronic kidney disease applied to patients over the age of 80 has increased the number of referrals to Nephrology. However not all of these patients may benefit from its assessment. This study aims to analyze the evolution of ≥80 years old patients referred to Nephrology. Methods: Single-center study including patients ≥80 years old with eGFR <60 mL/min/1,73m2 who were referred to Nephrology consultation for the first time. Clinical and analytical parameters were collected retrospectively 12 months before the visit, and prospectively at baseline, and 12 and 24 months after the initial visit. We divided patients into two groups based on annual eGFR loss: progressors (>5 mL/min/1.73m2) and non-progressors (≤5 mL/min/1,73m2). Results: A total of 318 patients were included, mean age was 84,9 ± 4 (80-97) years. Baseline serum creatinine was 1,65 ± 0,62 mg/dL, eGRF 35 (28-42) mL/min/1,73, and albumin/creatinine ratio 36 (7-229) mg/g. 55,7% of the patients met the definition of progressor at baseline (initial-progressors), 26,3% were progressors after a 12-month follow-up and 13,4% after 24 months. 21,2% and 11,4% of initial-progressors met this definition at 12 and 24 month follow up. The main risk factor for progression was albuminuria. No relationship was found between the nephrologist intervention and the evolution of renal function among initial non-progressors. Conclusion: Elderly patients who have stable renal function at the time of referral will continue to have stable renal function over the subsequent 24 months and thus may not need to be referred to a nephrologist.

Elastic Modulus of Woven Bone: Correlation with Evolution of Porosity and X-ray Greyscale.

The woven bone created during the healing of bone regeneration processes is characterized as being extremely inhomogeneous and having a variable stiffness that increases with time. Therefore, it is important to study how the mechanical properties of woven bone are dependent on its microarchitecture and especially on its porosity and mineral content. The porosity and the x-ray greyscale of specimens taken from bone transport studies in sheep were assessed by means of ex vivo imaging. Our study demonstrates that the porosity of the woven bone in the distraction area diminishes during the healing process from 73.3% 35 days after surgery to 31.9% 525 days after surgery. In addition, the woven bone's porosity is negatively correlated with its Young's modulus. The x-ray greyscale, was measured as an indicator of the level of mineralization of the woven bone. Greyscale index has been demonstrated to be inversely proportional to porosity and to increase to up to 60-80% of the level in cortical bone. The results of this study may contribute to the development of micromechanical models of woven bone and improvements in in silico modelling.

ß2-Glycoprotein I/IgA Immune Complexes: A Marker to Predict Thrombosis After Renal Transplantation in Patients With Antiphospholipid Antibodies.

BACKGROUND: Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to ß2-glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers. METHODS: We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-ß2-glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months. RESULTS: In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 (P<0.001) and 8.6% in the control group (P<0.001). The incidence of graft thrombosis in group 1 (31.2%) was significantly higher than that observed in group 2 (3.3%, P<0.001) and the control group (2.6%, P<0.001). In a multivariate analysis, the presence of B2A-CIC was an independent variable to experience any type of posttransplant thrombosis (hazard ratio, 6.72; 95% confidence interval, 4.81-9.37) and, prominently, for graft thrombosis (hazard ratio, 14.75; 95% confidence interval, 9.11-23.89). No significant differences were found between B2A-CIC-negative and control group patients. CONCLUSIONS: The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC-negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC-positive patients.

The Presence of Pretransplant Antiphospholipid Antibodies IgA Anti-ß-2-Glycoprotein I as a Predictor of Graft Thrombosis After Renal Transplantation.

BACKGROUND: Vessel thrombosis is a severe complication after renal transplantation. Antibodies anti-ß-2 glycoprotein-I of IgA isotype (IgA-aB2GP1) have been linked to thrombotic events and mortality in hemodialysis patients. METHODS: All kidney transplanted patients from 2000 to 2011 (n = 1375) in our hospital were followed up for 2 years, evaluating 3 time periods. RESULTS: At transplantation, 401 patients were positive for IgA-aB2GPI (29.2%, group 1), and the remaining patients were negative (group 2). Graft loss at 6 months posttransplantation was higher in group 1 (18% vs 7.2%; P < 0.001). The most frequent cause of early graft loss was vessel thrombosis, especially in group 1 (12.2% vs 2.6% of patients; P < 0.001). In fact, vessel thrombosis was the most important cause of graft loss in the 3 time periods, irrespective of demographic changes and introduction of transplantation with asystolic donors.Notably, IgA-aB2GP1 was an independent risk factor for graft thrombosis (odds ratio, 5.047; P < 0.001). Furthermore, the presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. Mortality at 24 months was also higher in group 1. CONCLUSIONS: In conclusion, pretransplant IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Further research should be made on whether anticoagulation in antibody-positive patients could ameliorate this catastrophic complication.

Association of early kidney allograft failure with preformed IgA antibodies to ß2-glycoprotein I.

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti-ß2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.

Renal transplantation dramatically reduces IgA anti-beta-2-glycoprotein I antibodies in patients with endstage renal disease.

IgA anti-beta-2-glycoprotein I (aB2GPI) antibodies have been related to vascular pathology in the general population and mainly in hemodialyzed patients (prevalence 33%) in whom an elevated incidence of thrombosis and mortality is found. In this paper we have studied the presence of IgA aB2GPI antibodies at pretransplant and their evolution after transplantation with a cross-sectional-based follow-up study of a cohort of 288 endstage renal disease (ESRD) patients treated with kidney transplantation. Pretransplant IgA aB2GPI levels were elevated 31.7 ± 4.2 U/mL without differences in age or type of dialysis. Patients with different etiologies of ESRD showed higher levels of IgA aB2GPI than blood donors, except the groups of non-IgA glomerular disease and systemic erythematosus lupus, whose nonsignificant differences were observed. IgA aB2GPI antibodies dropped immediately after transplantation (10.7 ± 1.0 U/mL, P < 0.0001), coinciding with a high degree of immunosuppression, and remained significantly lower than that observed in pretransplant status. Prevalence of patients with elevated antibodies was also less in transplanted patients (8.9% versus 30.4%, P < 0.0001). Among, positivity for IgA aB2GPI was higher than in patients who had received their first transplant that those were retransplanted. This finding could have important clinical implications and can suggest new therapeutic strategies in patients with IgA aB2GPI antibodies.

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease.

BACKGROUND: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). METHODS: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. RESULTS: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. CONCLUSIONS: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients.

IgA antibodies against ß2 glycoprotein I in hemodialysis patients are an independent risk factor for mortality.

Cardiovascular complications are the most important cause of death in patients on dialysis with end-stage renal disease. Antibodies reacting with ß-glycoprotein I seem to play a pathogenic role in antiphospholipid syndrome and stroke and are involved in the origin of atherosclerosis. Here we evaluated the presence of anticardiolipin and anti-ß-glycoprotein I antibodies together with other vascular risk factors and their relationship with mortality and cardiovascular morbidity in a cohort of 124 hemodialysis patients prospectively followed for 2 years. Of these, 41 patients were significantly positive for IgA anti-ß-glycoprotein I, and the remaining had normal values. At 24 months, overall and cardiovascular mortality and thrombotic events were all significantly higher in patients with high anti-ß-glycoprotein I antibodies. Multivariate analysis using Cox regression modeling found that age, hypoalbuminemia, use of dialysis catheters, and IgA ß-glycoprotein I antibodies were independent risk factors for death. Thus, IgA antibodies to ß-glycoprotein I are detrimental to the clinical outcome of hemodialysis patients.