Aim. To describe prognostic meaning of cardiac and other principal clinical manifestations of systemic AL-amyloidosis in their interrelations. Material and methods. It has been made long-time survival analysis of 147 patients with systemic AL-amyloidosis. In the special investigation group (n=58) of AL (n=55) and ATTR (n=3) amyloidotic cardiopathy patients there were evaluated prognostically important structural and functional changes in myocardium with standard and impulse-wave tissue dopplerometric echocardiography in comparison with NTproBNP serum levels. Results. Even though significantly increased nowadays surviving of AL-amylodotic patients (Me=90 months) it has been found that as at previously time orthostatic hypotension and amyloid cardiopathy are being most severe initial syndromes (median 25 months), but after 1 year from diagnosis influence of these syndromes on surviving had decreased and most low surviving was more common in patients with CKD 3-5 (median 28 months). Influence of CKD 3-5 on surviving was associated predominantly with intracardial hemodynamics deterioration. Together with decreased systolic shortening strain rate (48,5%) decreased filtration rate (47,9%) was second of main factors contributing into NTproBNP increasing in effective multiple regression model (R=0,702, F(4,21)=5,095, p=0,005). NTproBNP level in less degree depended on renal clearance. Conclusion. Heart damage is one of the most prognostically unfavorable manifestations of systemic amyloidosis due to a sharp deterioration in the elastic properties of the myocardium, in the process of further development of amyloidosis, the leading factor in progression is the deterioration of the profile of cardiorenal interactions, the marker of which is the level of NTproBNP.

AIM To investigate an influence of the currently changed etiologic structure of AA-amyloidosis on the diagnosis and treatment tactics. MATERIALS AND METHODS In 110 patients with АА-amyloidosis followed during full disease duration (1 month 29 years) etiology, clinical manyfestations and approaches to diagnose and treatment of AA-amyloidosis were evaluated. With ELISA levels of amyloid precursor acute phase inflammation reactant SAA and neutrophil activity marker S100A12 were measured. RESULTS Among the most common causes of AA-amyloidosis at the present stage, in addition to RA (40.3%), a significant place is occupied by a group of diseases with a predominantly autoinflammatory mechanism (53.73%). To confirm the autoinflammatory mechanism of the predisposing disease it is recommended to study a highly sensitive parameter serum protein S100A12. An effective marker of the risk of AA-amyloidosis progression, especially in patients with subclinical activity of inflammatory disease, is a high level of production of amyloidogenic protein-a precursor of SAA.

The article presents the case report of a rare hereditary form of systemic ATTR-amyloidosis in Russian patient with a discussion of approaches to the diagnosis and treatment of this form, also based on the own experience in the management of such patients. Modern ideas about the pathogenesis of the disease as well as detailed information about the clinical manifestations of amyloid cardiopathy and of other organs are presented. The nature of structural and hemodynamic changes in the heart is discussed on the basis of experience, including own, ultrasound examination of the heart in patients with amyloidosis, especially the article focuses the reader's attention on the true infiltrative nature of transtiretin amyloid cardiopathy in contrast to AL-amyloidosis, in which there is a significant inflammatory component that determines a more unfavorable natural course of AL-amyloidosis of the heart. The article discusses the differential diagnosis of different types of amyloidosis, the diagnostic difficulties associated with weak congophilia of transtiretin amyloidosis and at the same time substantiates the need for morphological verification of the diagnosis. Modern methods of treatment of ATTR-amyloidosis are discussed.

Особенности эволюции и прогностическое значение поражения сердца у больных системным AL-амилоидозомВ.В.Рамеев, Л.В.Козловская, А

"The critical role of chronic kidney disease in the progression of AL-amyloid cardiopathy." Amyloid, 26(sup1), pp. 109–110

Cardiac involvement is the most important cause of death in light chain amyloidosis (AL) and its early diagnosis is a major issue for therapeutic strategy.Gold diagnostic standards are either invasive (cardiac biopsy) or not widely available (cardiac MRI).We aim to compare diagnostic value of various diagnostic tools in this setting.Methods: Following diagnostic tests were performed after first diagnosis of AL amyloidogenic disorder: clinical examination, blood testing of BNP and troponin I, EKG, echocardiography, 24-hours EKG Holter, cardiac MRI, cardiopulmonary test.Cut-offs were chosen from literature for parameters with continuous values.Final diagnosis of cardiac amyloidois (CA) was done either by MRI if diffuse late enhancement was present or by an expert consensus (3 clinicians) using all medical files.Diagnostic values of tests as well as their combination were calculated.Results: Among sixty-four consecutive patients (65±10 years, 21 with multiple myeloma and 43 with MGUS), final diagnosis of CA was done in 42 patients.Renal, digestive and neurologic AL involvements were present in 43%, 21% and 19% respectively of patients with CA.The table shows diagnostic values of EKG, BNP and echography as well as their combinations.Usefulness of troponin, holter or stress test was less relevant.

AIM To study correlations between accumulation of angiogenesis molecular factors (hypoxia-inducible factor-1alpha - HIF-1alpha, vascular endothelial growth factor - VEGF, thrombospondin - TSP-1) in kidney biopsy tissue from chronic glomerulonephritis (CGN) patients and severity of nephrosclerosis, obliteration of renal capillary bed, filtration dysfunction and anemia. MATERIAL AND METHODS We examined 22 patients with marked proteinuria (2.77; 5.7, mean 4.2 g/ day). Half of the patients had nephrotic syndrome. Glomerular filtration rate (GFR) by Cochroft-Golt formula was 68 (53;84) ml/min/1.73 m2. According to renal biopsy findings, CGN was detected in 19 patients, 2 patients had lupus nephritis (LN), 1 patient had renal amyloidosis. Nineteen CGN patients were divided into two groups by nephrosclerosis severity: group 1-7 patients with moderate nephrosclerosis, group 2-12 patients with severe nephrosclerosis. Cryostate sections of renal biopsy tissue samples were studied immunohistochemically using monoclonal antibodies to HIF-1alpha, VEGF, TSP-1, CD34. The reaction intensity was assessed by 6-point scale semiquantitative method. RESULTS Response to HIF-1alpha was stronger in the tubular epithelium than in glomeruli. No correlation was observed between accumulation of HIF-1alpha in the glomeruli and tubular epithelium. Intensity of glomerular staining correlated with severity of proteinuria (Rs = 0.63, p < 0.05), intensity of HIF-1alpha accumulation in tubular epithelium correlated with duration of the kidney disease (Rs = 0.74, p < 0.001), duration of persistent arterial hypertension (Rs = 0.68, p < 0.05) and severity of nephrosclerosis. VEGF and TSP-1 were found in equal quantity both in the glomeruli and renal interstitium. CGN patients with marked nephrosclerosis had lower accumulation of VEGF and higher TSP-1 in the interstitium. No correlation was found between intensity of tubular epithelium response to HIF-1alpha and accumulation of VEGF in the interstitium. Patients with severe nephrosclerosis demonstrated weaker staining of tubulointerstitium to CD34, reflecting the degree of its vascularisation. Significant correlation between CD34 and expression of HIF-1alpha, VEGF, TSP-1 was not registered. In patients with low intensity of tubular epithelial staining to HIF-1alpha (less than 2 points) anemia was detected in 63% versus 18% in patients with more intensive accumulation. CONCLUSION CGN progression is associated with development of renal tubulointerstitial ischemia. High tubular production of HIF-1alpha was not accompanied with activation of VEGF accumulation in renal interstitium but was associated with reduced risk of anemia in CGN patients with manifest nephrosclerosis.