Simona Stancu

Can the Response to Iron Therapy Be Predicted in Anemic Nondialysis Patients with Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Anemia is iron responsive in 30 to 50% of nondialysis patients with chronic kidney disease (CKD), but the utility of bone marrow iron stores and peripheral iron indices to predict the erythropoietic response is not settled. We investigated the accuracy of peripheral and central iron indices to predict the response to intravenous iron in nondialysis patients with CKD and anemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A diagnostic study was conducted on 100 nondialysis patients who had CKD and anemia and were erythropoiesis-stimulating agent and iron naive. Bone marrow iron stores were evaluated by aspiration. Hemoglobin, transferrin saturation index (TSAT), and ferritin were measured at baseline and 1 month after 1000 mg of intravenous iron sucrose. Posttest predictive values for the erythropoietic response (> or =1-g/dl increase in hemoglobin) of peripheral and central iron indices were calculated. RESULTS The erythropoietic response was noted in a higher proportion in bone marrow iron-deplete than in iron-replete patients (63 versus 30%). Peripheral iron indices had a moderate accuracy in predicting response. The positive (PPV) and negative predictive values (NPV) were 76 and 72% for a TSAT of 15% and 74 and 70% for a ferritin of 75 ng/ml, respectively. In the final logistic regression model, including TSAT and ferritin, the chances of a positive response increased by 7% for each 1% decrease in TSAT. CONCLUSIONS Because an erythropoietic response is seen in half of patients and even one third of those with iron-replete stores responded whereas peripheral indices had only a moderate utility in predicting response, the therapeutic trial to intravenous iron seems to be a useful tool in the management of anemia in nondialysis patients with CKD.

Is hepcidin-25 a clinically relevant parameter for the iron status in hemodialysis patients?

BACKGROUND Accumulating data suggest potential clinical relevant relationships between hepcidin-25 levels, iron stores, erythropoiesis effectiveness, and epoetin dose. The immunometric methods and mass spectroscopy are currently used to measure hepcidin-25, but no standard exists, and values, although similar in trends, differ in absolute value. OBJECTIVE To investigate hepcidin levels and their relationship with peripheral iron indices, inflammation, and anemia therapy in patients on hemodialysis (HD). METHODS A cross-sectional study in 78 patients from a single HD center. Hepcidin-25 was measured with enzyme-linked immunosorbent assay (ELISA), using a commercial kit (Bachem, UK). RESULTS Hepcidin-25 levels were similar to those previously reported in studies using the same antibody (median 113 [95% CI; 107-122 ng/mL]) and significant but weak correlations of hepcidin with transferrin (R2=0.06; p<0.04) and ferritin (R2=0.09; p<0.01) were found. A model of multiple regression analysis explained 57% of variation along hepcidin quartiles. Lower hepcidin levels were associated with higher transferrin levels (odds ratio 1.05 [1.01-1.09]), bigger iron doses (odds ratio 1.09 [1.02-1.15]), and an increased darbepoetin resistance index (odds ratio 4.3E+15 [11.15-1.6E+30]). An elevated serum C reactive protein was associated with increased hepcidin levels (odds ratio 0.70 [0.49-0.99]), while a higher ultrafiltration volume (odds ratio 4.30 [1.28-14.51]) and the male sex (odds ratio 0.04 [0.00-0.80]) were related to lower hepcidin levels. LIMITS Cohort number and composition. Hepcidin-25 ELISA assay. CONCLUSION A low hepcidin level in hemodialysis patients with high epoetin resistance index could be a useful marker of iron-restricted erythropoiesis, but confirmation by a therapeutical trial is necessary.

Validation study of Oxford Classification of IgA Nephropathy: the significance of extracapillary hypercellularity and mesangial IgG immunostaining

The Oxford classification (OC) of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as predictors of outcome. We aimed to validate the OC and to investigate the clinical significance of extracapillary hypercellularity and IgG immunostaining. We examined the renal outcome at December 31, 2014, of 121 adult patients with biopsy proven primary IgAN between 2003 and 2013. The primary endpoint was doubling of serum creatinine or renal replacement therapy initiation. The mean observation period was 59.7 months. Thirty‐one percent of the patients presented with a grade of extracapillary hypercellularity. In comparison with the group with no crescents, they had higher grade of inflammation, lower eGFR and increased proteinuria. There were no differences between the IgA and IgA&IgG immunostaining groups regarding the disease progression risk factors. Mean kidney survival time for the entire cohort was 10.6 (9.1, 12.0) years. In the Cox regression model, the independent predictors of decreased renal survival were eGFR at time of biopsy, S1 and the presence of crescents. Our study showed that extracapillary proliferation and S1 had the greatest importance in establishing the renal prognosis of patients with IgAN.

Tuberculin Skin Test, Interferon-gamma Assay, and T Cells Subpopulations in Hemodialysis Patients

OBJECTIVE To examine and compare the responses of hemodialysis (HD) patients to Mycobacterium tuberculosis antigens by using the tuberculin skin test (TST) and an interferon gamma assay (IFN-TB), and to investigate the relationship between T cells subpopulations and tests results. Observational, prospective, diagnostic study conducted in a HD center in a country with high prevalence of tuberculosis. PATIENTS 195 patients on maintenance HD who consented to participate in this study; 187 (6 were excluded for refusing TST and 2 for indeterminate responses to IFN-TB) were HIV negative, vaccinated with the Bacille Calmette-Guerin vaccine, and without any signs of active tuberculosis, were selected. METHODS Similar to the Mantoux method, 10 IU tuberculin was used for the TST. An IFN-gamma assay specific for Mycobacterium tuberculosis antigens and phytohemagglutinin was carried out. Flow cytometry analysis of peripheral lymphocytes was also performed. RESULTS TST and IFN-TB results were found to be positive (44% and 53%, respectively) or negative (32% and 47%, respectively) in similar proportions. Results were in agreement in 71% of positive and 58% of negative tests. IFN-gamma levels were found to be higher in patients with a positive TST. All cell counts and CD4/CD8 were found to be higher in TST-positive patients, whereas only total lymphocytes count and CD4/CD8 were reported to be high in IFN-TB-positive patients. A model of multivariable linear regression including cell counts explained 16% of the mitogen-induced IFN-gamma production (F = 5,11; P = .0003). The majority of subjects with positive tests were younger, in most cases male, belonged to the Roma ethnic group, had a shorter HD vintage, and a better nutritional status. CONCLUSIONS TST and IFN-gamma production stimulated by Mycobacterium tuberculosis antigens rely on patients immune status, which could be influenced by either individual (age, gender), dialysis-related (HD vintage), or nutritional factors. In addition, the diagnostic utility for tuberculosis is similar and moderate in HD patients.

Subclinical cardiovascular disease markers and vitamin D deficiency in non-dialysis chronic kidney disease patients.

Introduction Since 25-hydroxyvitamin D (25(OH)D) deficiency has been linked to an increased risk for cardiovascular disease (CVD) in the hemodialysis population, we aimed to determine the relationship between serum 25(OH)D level and markers of subclinical CVD in non-dialysis chronic kidney disease (CKD) patients. Material and methods This cross-sectional, single-center study prospectively enrolled 87 clinically stable CKD patients (median age: 61 (57–66) years, 51% male, median estimated glomerular filtration rate (eGFR): 32 (27–37) ml/min). Five markers of subclinical CVD were assessed: intima-media thickness, abdominal aortic calcifications (AAC) using the Kauppila score, cardio-ankle vascular index, ankle-brachial index (ABI) and interventricular septum thickness. Results Vascular (37%), glomerular (23%) and interstitial (18%) nephropathies were the main causes of CKD. 25(OH)D had a median value of 14 (12.5–17.1) ng/ml, and its levels decreased with eGFR (rs = 0.19; p = 0.04). Patients with 25(OH)D deficiency (54%) were older, had a higher serum alkaline phosphatase level, lower ABI and higher AAC score. There were no differences between the two groups regarding other traditional or non-traditional risk factors for atherosclerosis. The association between subclinical CVD markers and 25(OH)D was further evaluated in multivariable binomial logistic regression models adjusted for CV risk factors. Lower 25(OH)D level was retained as an independent predictor only for pathological ABI. Conclusions This is the first study to evaluate the relationship between a large set of subclinical CVD markers and 25(OH)D deficiency in non-dialysis CKD patients. We found that hypovitaminosis D is associated with subclinical peripheral arterial disease, independently of other cardiovascular risk factors.