IL 6 but not TNF is linked to coronary artery calcification in patients with chronic kidney disease.

INTRODUCTION: Patients with chronic kidney disease (CKD) have a high risk of death mainly due to cardiovascular diseases (CVD). Early risk identification may allow interventions and prevention of fatal events. OBJECTIVES: The study aim was to assess the usefulness of selected CVD biomarkers as predictors of 5-year mortality in patients with different CKD stages. PATIENTS AND METHODS: Study included 57 CKD patients: 38 in stage 5 (ESRD), 19 in stage 3 and 4 (CKD3-4), and 19 healthy controls. Blood samples were obtained once to measure fetuin A, adiponectin, leptin, tumor necrosis factor (TNF), interleukin-6 (IL-6), metalloproteinase-9 (MMP9), intracellular-1 (ICAM1) and vascular-1 (VCAM1) adhesion molecules (ELISA or Luminex platform). Computed tomography was performed to assess the calcium score (CS). Patients were prospectively followed for 5 years to evaluate their all-cause mortality. RESULTS: Serum VCAM1, TNF and IL-6 were significantly higher in more advanced CKD stages. VCAM1 correlated significantly with ICAM1, TNF and IL-6. TNF and IL-6 were also significantly correlated with each other. No significant changes were detected for other markers. IL-6 correlated significantly with CS, age, renal function and CRP. Elevated CS and IL-6 increased over 3 times the 5-year all-cause and cardiovascular mortality risks in patients with CKD or ESRD at baseline. CONCLUSIONS: IL-6 and CS were significantly associated with 5-year risk of all-cause mortality in CKD patients. Our study suggests an involvement of chronic inflammation linked to coronary artery calcification that is likely to contribute to the cardiovascular mortality in patients with impaired renal function.

A Stepwise Screening Protocol for Multiple Myeloma.

BACKGROUND: Monoclonal gammopathies and multiple myeloma should be screened in the primary care setting. METHODS: The screening strategy consisted of an initial interview supported with the analysis of basic laboratory test results and the increasing laboratory workload in the following steps was developed based on characteristics of patients with multiple myeloma. RESULTS: The developed 3-step screening protocol includes evaluation of myeloma-related bone disease, two renal function markers, and three hematologic markers. In the second step, the erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP) were cross-tabulated to identify persons qualifying for confirmation of the presence of monoclonal component. Patients with diagnosed monoclonal gammopathy should be referred to a specialized center to confirm the diagnosis. The screening protocol testing identified 900 patients with increased ESR and normal level of CRP and 94 of them (10.4%) had positive immunofixation. CONCLUSIONS: The proposed screening strategy resulted in an efficient diagnosis of monoclonal gammopathy. The stepwise approach rationalized the diagnostic workload and cost of screening. The protocol would support primary care physicians, standardizing the knowledge about the clinical manifestation of multiple myeloma and the method of evaluation of symptoms and diagnostic test results.

Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality.

BACKGROUND: Chronic kidney disease (CKD) is associated with cardiovascular disease (CKD), mineral and bone disorder (CKD-MBD) and high mortality. Bone-related factors such as osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF23) were linked to cardiovascular complications of CKD and are expected to have predictive value in CKD patients. PURPOSE: The aim of this study was to assess the relationship of OPN, OC, OPG and FGF23 to clinical characteristics and to evaluate their ability to predict mortality in patients with different CKD stages. METHODS: The following study groups were enrolled: subjects with end-stage renal disease (38 ESRD), CKD stages 3 and 4 (19 CKD3-4) and non-CKD controls (19), respectively. Blood was withdrawn once to perform the measurements and cardiac computed tomography was used to evaluate coronary calcium score (CS). Patients were followed for 5 years for the ascertainment of their all-cause mortality. RESULTS: Serum OPN, OC and OPG concentrations increased significantly along with the progression of renal disease. We found a significant positive correlation among these proteins. Additionally, OPN and OPG were significantly and positively correlated to CS. Serum OPG revealed the strongest correlation to the calcium turnover markers of GFR decline and was significantly associated with an increased risk of death in subjects with CKD3-4 or ESRD (HR 5.8, CI 95%). CONCLUSION: Single measurement of osteoprotegerin is associated with 5-year all-cause mortality in patients with CKD3-4 or ESRD. We suggest assessing its concentration, preferably in combination with calcium score, to stratify mortality risks in CKD patients.

FRAX prognostic and intervention thresholds in the management of major bone fractures in hemodialysis patients: A two-year prospective multicenter cohort study.

PURPOSE: The usefulness of FRAX in predicting major bone fractures in patients with end-stage kidney disease on maintenance hemodialysis treatment has been confirmed in previous studies. For meaningful clinical use, the prognostic and intervention FRAX thresholds need to be established. METHODS: The primary aim of our study was to calculate the optimal cut-off point of FRAX for the best prediction of an increased bone fracture risk in dialysis patients and additionally, to propose its intervention threshold, indicating the need for antifracture pharmacological treatment. The study included 718 hemodialysis patients, who were followed up for two years. Thirty low-energy major bone fractures were diagnosed during the study period. We used the Polish version of FRAX (without the DXA examination) and some particular variables of the FRAX calculator. The optimal cut-off point for prediction of an increased major bone fracture risk was based on the analysis of the sensitivity and specificity curves of FRAX. RESULTS: The analysis revealed FRAX >5% (sensitivity of 70.0%, specificity of 69.8%) as the prognostic threshold for major bone fractures. Its sensitivity for bone fracture prediction was significantly higher, but specificity lower than those of FRAX ≥10%, used in general Polish population. The reason for this can be an underestimation of bone fracture risk with FRAX in dialysis patients. CONCLUSIONS: We conclude that the FRAX prognostic threshold for identification of an increased risk of major bone fractures in hemodialysis patients is >5%. We propose to use this specific value of FRAX as an intervention threshold for pharmacological antifracture treatment in hemodialysis patients.

Value of multilocus genetic risk score for atrial fibrillation in end-stage kidney disease patients in a Polish population.

Genetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.

Rhythm control versus rate control in patients with persistent atrial fibrillation. Results of the HOT CAFE Polish Study.

BACKGROUND: Patients with atrial fibrillation (AF) can be managed either by maintaining sinus rhythm using antiarrhythmic drugs and/or electrical cardioversion, or by leaving patients in AF and controlling ventricular rate without attempts to restore sinus rhythm. Which of these two strategies is superior, has not yet been definitively established. AIM: HOT CAFE Polish Study (How To Treat Chronic Atrial Fibrillation) was designed to evaluate in a randomised, multicentre and prospective manner the risks and advantages of two therapeutical strategies - rate control or rhythm control, in patients with persistent AF. METHODS: The study group consisted of 205 patients (71 females and 134 males; mean age 60.8+/-11.2 years) with a mean time of AF duration of 273.7+/-112.4 days; 101 patients were randomly assigned to rate control (Group I) whereas 104 patients were randomised to sinus rhythm (SR) restoration by DC cardioversion (CV) and subsequent antiarrhythmic drug treatment (Group II). At the end of follow-up (12 months) SR was present in 75% of patients. RESULTS: The incidence of hospital admissions was higher in group II in comparison to group I (12% vs 74%; p<0.001). Mortality was similar in both groups (1.0% versus 2.9%, NS). In both groups a significant improvement of heart failure symptoms was observed during the first 2 months (p<0.02 and p<0.001). In group II exercise tolerability measured by maximal workload during treadmill test significantly improved compared with baseline (5.2+/-5.1 vs 7.6+/-3.3 MET; p<0.0001). In patients in whom SR was restored, the left ventricular function improved and an increase in the shortening fraction was observed (29+/-7% vs 31+/-7%; p<0.01). No thromboembolic complications were observed in patients left with AF. Three patients from group II suffered ischaemic stroke; in two cases stroke was associated with CV whereas in the third patient - with late AF recurrence. CONCLUSIONS: The HOT CAFE Polish Study did not reveal significant differences in mortality between the two treatment strategies in patients with persistent AF. Although patients with SR had better improvement in some haemodynamical parameters, the hospitalisation rate was higher and the incidence of stroke was not reduced compared with the rate control group.

[Metoclopramide test in the patients with hyperprolactinemia due to end-stage renal failure]. / Test z metoklopramidem u chorych z hiperprolaktynemia w przebiegu schylkowej niewydolnosci nerek.

UNLABELLED: Evaluation of metoclopramide (MTC) test values in end-stage renal disease patients undergoing hemodialysis with different level of hyperprolactinemia was aim of the study. Clinical value of application of the MTC test and influence of different laboratory and clinical factors including erytropoietin treatment were examined. Sixty-eight hemodialysed patients (31 male and 37 female) aged 20-74 yr. (medium 48 +/- 13 yr.) underwent the MTC test, the control group consisted of 8 healthy volunteers (4 male and 4 female). 10mg of MTC was given i.v. and serum level of PRL was determined in 0, 30 and 60 min. after injection. Significant suppression of PRL stimulation in the patients was shown as compared with the controls after 30 min and delayed decrease of the curve values was found. An increase in the PRL level after 60 min in investigated group was lower than in control. Lower relative enhance of PRL level in 30 min was found and slower decrease after 60 min. Despite the slower decrease PRL level was lower in the patients than in the controls after 60 min. The highest relative increase in PRL level after 30 min was observed in the patients with lowest initial level of PRL (r=-0.471; p<0.001). Erytropoietin administration improved the response in the test (p=0.005) without relationship to the duration of erytropoietin treatment. There was influence of hemoglobin level on the results of the test. CONCLUSIONS: Results of the MTC test in end-stage renal disease patients is inadequate and the PRL response is diminished. Diagnostic value of the test in end-stage renal disease patients is low. Erytropoietin administration improves although not to the normal values the results of the MTC test.

[Management of hyperthyroidism with radioactive iodine in end-stage renal disease patients undergoing dialysis]. / Jod radioaktywny (I131) w leczeniu nadczynnosci tarczycy u chorych przewlekle dializowanych z powodu schylkowej niewydolnosci nerek.

Although, the abnormal thyroid hormone production and metabolism are relatively common, hyperthyroidism is a very unusual condition. The diagnosis may be difficult because of similar signs and symptoms as in uremia. To our knowledge till now only 18 well documented cases have been reported, 8 of them successfully treated with radioactive iodine. We report here the results of radioiodine treatment, performed in 6 patients, 5 with toxic multinodular goiter and one with Graves' disease. Three patients were initially treated with antithyroid drugs, but they were discontinued 20 days before radioiodine treatment. A progressive fall of the thyroid function tests was observed. Of 6 treated patients 3 became euthyroid and 3 developed hypothyroidism.