Olomouc, Czech Republic
Olomouc, Czech Republic

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Background. The diagnostics and treatment of multiple myeloma (MM) requires precise analysis of serum immunoglobulins, which might be limited by the sensitivity of standard examination methods. Hevylite™ method enables quantitative analysis of heavy/light chain pairs (HLC) of normal and tumor IgG and IgA immunoglobulin and their ratio (HLC-r). The aim of the study was to assess the contribution of Hevylite™ method in the diagnostics of MM in comparison with nephelometry (NEF), standard protein electrophoresis (SPE), immunofixation electrophoresis (IFE) and the examination of serum free light chains (FLC) of immunoglobulin using Freelite™ test and heavy/light chain pairs of immunoglobulin (HLC) using Hevylite™. Methods. Using the methods Hevylite™, NEF, SPE, IFE and Freelite™, we examined a cohort of 134 individuals fulfilling the International Myeloma Working Group (IMWG) criteria. 96 patients were of IgG and 38 of IgA type. Results. The levels of HLCkappa (K) and HLC-lambda (L), as well as HLC-r were independent of age and gender. Abnormal HLC levels were present in 84-100%, pathological HLC-r was in 92-100% cases based on MIg isotype. We found strong positive correlation between IgG and IgA (NEF) and the sum of HLC IgG-K + IgG-L (Hevylite™) (r = 0.80, p <0.0001) and HLC IgA-K + IgA-L (r = 0.75, p < 0.0001). Very strong positive correlation was between the concentration of MIg (SPE) and the levels of HLC (Hevylite™) in IgG-K (r = 0.73), IgG-L (r = 0.76), IgA-K (r = 0.70) and IgA-L (r = 0.89), p < 0,0001. Systematic difference between Hevylite™ vs. MIg (SPE) was confirmed by Bland-Altmann test in the case of HLC IgA-K and IgA-L (not HLC IgG-K and IgG-L), and in the correlation of HLC with IgG and IgA (NEF). The most significant correlation between SPE (patients with < 15 g/L) vs. Hevylite™ was found within the analysis of HLC IgG-K+ IgA-K (r = 0.85, p < 0.0001), and in the whole cohort of MM patients, i.e. IgG + IgA-kappa and lambda (r = 0.76, p < 0.0001), confirmed by Bland-Altmann test. Tight positive correlation was between HLC-r and index of monoclonality FLC-K/L in MM of IgG and IgA type MM (p < 0.0001). Conclusion. Hevylite™ method, especially the assessment of HLC-r of IgA type MM is more sensitive in comparison with SPE evaluated by NEF, and increases the diagnostic sensitivity and the extent of tumor mass examination. Despite its limitation in the case of high levels of IgG type MIg, Hevylite™ technique has a promising potential to enrich the standard analytic tools as it enables to assess the concentration and ratio of the levels of both tumor and physiological immunoglobulins e.g. depth of immunoparesis, valid especially in MM with low levels of MIg.


Vaverkova Dr. H.,III. interni klinika nefrologicka
Interni Medicina pro Praxi | Year: 2013

The risk of death from cardiovascular disease is increased already in early stages of chronic kidney disease (CKD), and increases significantly in more advanced stages. This risk is comparable to that in diabetes and pre-existing ischemic heart disease. The increased cardiovascular risk in CKD is due to both traditional and untraditional risk factors, including dyslipidemia. Dyslipidemia is modifiable and should be treated. Statins slow the progression of CKD and have a beneficial effect on proteinuria. Statins reduce all-cause and cardiovascular mortality as well as the occurrence of cardiovascular events in early stages of CKD (stages 1 to 4); in stage 5D, however, they only have a minor effect on the above-mentioned events. The benefit of statin treatment in stage 5D in terms of cardiovascular events can likely be expected only in persons with increased LDL cholesterol. Fenofibrate favorably affects the progression of albuminuria in type 2 diabetics. The largest reduction in cardiovascular events and cardiovascular mortality in the FIELD study with fenofibrate was achieved in diabetics with stage 3 CKD. The dose of hypolipidemic agents (except for atorvastatin and ezetimibe) must be adjusted to the degree of impaired renal function. Roughly 10% of the population have CKD and only a small proportion of them are aware of it. Early stages of CKD are asymptomatic and CKD is often diagnosed incidentally on examination by a general practitioner or internist. Routine use of estimated glomerular filtration rate (eGFR) and determination of microalbuminuria in at-risk individuals (particularly diabetic and hypertensive patients) could identify a large number of people in the population who can benefit from hypolipidemic therapy.


Minarik J.,III. interni klinika nefrologicka | Pika T.,III. interni klinika nefrologicka | Bacovsky J.,III. interni klinika nefrologicka | Scudla V.,III. interni klinika nefrologicka
Interni Medicina pro Praxi | Year: 2012

The aim of our paper is to present cryoglobulinemia, its types, and clinical manifestation. We describe a case report of a patient with newly diagnosed cryoglobulinemic vasculitis associated with multiple myeloma. Mild symptoms of cryoglobulinemia, however, were present and unrecognized for more than 10 years. We describe the presenting symptoms, laboratory findings an examinations that lead to diagnosis confirmation. We also aim at the pitfalls of diagnostics as well as the treatment of patients with cryoglobulinemia. In routine practice, it is necessary to know the symptoms of the disease and in legitimate casesto think of the possibility of cryoglobulinemia. The blood samples should be transported warm, at body temperature.


Zurek M.,III. Interni Klinika Nefrologicka | Horak P.,III. Interni Klinika Nefrologicka
Osteologicky Bulletin | Year: 2016

Type 1 and 2 diabetes mellitus is a condition associated with an increased risk for the development of low-energy fractures. Bone mineral density values are usually decreased in type 1 diabetics and normal or increased in type 2 diabetics, as compared with the general population. In type 1 and 2 diabetes mellitus, impaired microarchitecture of the bone tissue may be diagnosed using high-resolution peripheral quantitative computed tomography or trabecular bone score. New bone formation is reduced in both diabetes types. Patients with diabetes and a history of low-energy fractures or those with densitometry results suggesting osteoporosis in accordance with the World Health Organization definition are at increased risk of fractures. Since the use of specific drugs for this particular condition is not supported by long-term data, drugs are used that have been shown effective in postmenopausal osteoporosis by registration studies.


Skacelova M.,III. Interni Klinika Nefrologicka | Horak P.,III. Interni Klinika Nefrologicka
Osteologicky Bulletin | Year: 2013

Male osteoporosis is a condition with an increasing incidence and relatively high mortality associated with fractures. A secondary etiology is quite common, mostly contributed to by deficiency of sex hormones (testosterone, estradiol), other diseases and medication use. Prior to treatment initiation, a secondary etiology should be clearly ruled out. A significant role in the prevention and treatment is played by modification of lifestyle factors (physical activity, smoking, alcohol consumption, etc.) and sufficient calcium and vitamin D supplementation. In the treatment of male osteoporosis, bisphosphonates are currently used. If taken regularly, they increase BMD of the lumbar spine and proximal femur and aid in reducing the risk of osteoporotic fractures. Drugs currently approved for use are alendronate, risedronate and zoledronic acid. Other drugs known to be effective in the treatment of male osteoporosis are strontium ranelate and teriparatide.


Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vessel-specific inflammatory enzyme playing a role in the formation of vulnerable, rupture-prone atherosclerotic plaques. Lp-PLA2 is believed to be a link between oxidative LDL modification and the inflammatory response by the arterial intima. Unlike high-sensitivity C-reactive protein (hs-CRP) and other inflammatory markers produced by the liver, Lp-PLA2 is not associated with BMI, shows substantially lower intra-individual variability and is more vessel-specific. Prospective primary and secondary prevention studies have shown Lp-PLA2 potential to predict coronary events and ischemic stroke even after adjustment to conventional risk factors and hs-CRP. It is for these reasons that this novel marker of inflammation could become an invaluable surrogate marker of increased cardiovascular risk, in particular in individuals at intermediate risk not indicated (by current guidelines) for adequate modification of conventional risk factors, in particular hyperlipidemia. Lp-PLA2 levels are decreased both by lifestyle modifications and most lipid-lowering agents. Darapladib, a selective Lp-PLA2 activity inhibitor, is currently being tested in a large morbi dity and mortality study STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) which could potentially document the causative role of this novel risk factor in the process of atherosclerosis.


Pika T.,III. Interni Klinika Nefrologicka | Minarik J.,III. Interni Klinika Nefrologicka | Lochman P.,Oddeleni Klinicke Biochemie a Imunogenetiky | Bacovsky J.,III. Interni Klinika Nefrologicka | Scudla V.,III. Interni Klinika Nefrologicka
Transfuze a Hematologie Dnes | Year: 2011

Introduction. Monoclonal gammopathy of undetermined significance (MGUS) is a potentially malignant condition associated with a certain degree of probable transformation into one of the malignant forms of monoclonal gammopathy (MG). Identifying possible predictive factors of malignant evolution is the focus of several research centres. Determining serum levels of free light chains (FLC) appears to be a relatively significant parameter, enabling the identification of persons at higher risk of malignant transformation. The report aims to present our own experience with determining FLC serum levels in a group of individuals with MGUS. Group and results. The monitored group numbered 191 persons with MGUS. Abnormal κ or λ FLC levels were detected in 119 (62.3%), and pathological values of the κ/λ index in 106 (55.5%) patients. During the six years of monitoring, 11 (5.7%) persons in total experienced transformation into a malignant form of MG, which corresponds approximately to a transformation rate of 0.95%/year in the whole group. Using the stratification system for MGUS based on the combination of quantity, monoclonal immunoglobulin isotype and the κ/λ index value, there were 56 (29.3%) persons in the low-risk group, 87 (45.5%) in the low-intermediate risk group, 45 (23.6%) in the high-intermediate risk group, and only 3 persons (1.6%) in the high-risk group. The transformation percentage for the individual groups corresponded to 0 vs. 4.5 vs. 13.3 vs. 33.3% over the course of 6 years. MGUS evolution was associated with increasing FLC levels and a change in the κ/λ index. Conclusion. The survey results have confirmed the practical benefits of testing FLC serum levels in persons with MGUS, particularly the positive contribution to risk stratification with identification of MGUS high risk forms, allowing early detection of malignant evolution and immediate initiation of adequate treatment.


Zurek M.,III. Interni Klinika Nefrologicka | Horak P.,III. Interni Klinika Nefrologicka
Osteologicky Bulletin | Year: 2016

Diabetes mellitus (DM) is a condition developing as a result of an absolute or relative lack of insulin. The missing anabolic effect of insulin plays a crucial role in the pathogenesis of osteoporosis in type 1 DM. High levels of glucose contribute to the development of diabetic osteopathy by a mechanism of non-enzymatic glycation, increase stress at a cellular level, stimulate production of reactive oxygen species and expression of anti-inflammatory cytokines and activate PPAR receptors, all leading to impaired differentiation of osteoblasts from mesenchymal stem cells. Mild systemic inflammation, present in type 2 DM, adversely affects bone remodeling. Central obesity with an increased volume of visceral adipose tissue is frequently seen in type 2 diabetics. The relationship between adipose tissue and bones is mediated by various mechanisms. Extraskeletal factors, in particular a higher risk of falls, further increase the risk for fractures in diabetics. Administration of anti-diabetic medication may affect the bones in both positive and negative manners.


Horak P.,III. interni klinika nefrologicka | Skacelova M.,III. interni klinika nefrologicka
Interni Medicina pro Praxi | Year: 2015

Strontium ranelate is an agent used for the treatment of postmenopausal osteoporosis in women and of male osteoporosis. Preclinical data suggest its dual action consisting in inhibiting bone resorption and stimulating bone formation. Strontium ranelate administration leads to a significant increase in bone mass. Changes in the bone density can be used to evaluate the adherence of patients and, in the case of strontium ranelate, to obtain a relatively accurate estimation of the reduction in fracture risk. Clinical studies have shown its effect on reducing the risk of both vertebral and non-vertebral fractures, including proximal femoral fractures. Currently, strontium ranelate is a second-line drug in the treatment of osteoporosis administered in the case of failure of, intolerance to, or contraindication to other drugs. Recently, its cardiovascular safety has been debated. The contraindications to its administration in patients with ischaemic heart disease or lower limb ischaemia and stroke were added to the 2013 version of product information. However, cohort and observational studies so far have failed to provide an unequivocal confirmation of the cardiovascular risk associated with its administration. It still remains a drug with a favourable risk-effect ratio, intended for osteoporosis treatment.


Apolipoproteins (Apo) are protein components of lipoprotein macromolecules. They fulfil various functions that can affect the destiny of lipoprotein particles, thus influencing the atherogenesis process. In terms of clinical practice, only the determination of ApoB has been of importance so far: ApoB is an indicator of the total number of atherogenic particles as well as a good surrogate marker of the number of small dense LDL (sdLDL). According to the ESC/EAS 2011 guidelines, ApoB should be considered an alternative risk marker in patients with combined hyperlipidemia, metabolic syndrome, diabetes and chronic kidney disease. In these patients, ApoB is also a secondary target indicator of treatment efficacy. Neither ApoA-1 nor the ApoB/ApoA-1 ratio is suitable for assessing treatment efficacy.

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