[Role of tubulin in the pathogenesis of fibrillary glomerulonephritis].

Fibrillary glomerulonephritis is a disease from a group of glomerular diseases with organized deposits. Its etiology and pathogenesis have not been studied. The paper deals with the clinical, morphological, immunohistochemical, and electron microscopic studies of 45 patients with fibrillary glomerulonephritis. The electron microscopic study revealed the microtubule pattern of fibrils in fibrillary glomerulonephritis. Comparative immunohistochemical analysis of the protein tubulin in nephrobiopsy specimens was made in patients with fibrillary glomerulonephritis and in those diagnosed as having minimal changes.

[Morphological and immunochemical features of nephropathies in multiple myeloma and severe renal failure].

AIM: To study the pathomorphology of kidneys in patients with multiple myeloma (MM) and severe renal failure (RF) and to compare the results of morphological, immunohistochemical, and electron microscopic examinations of nephrobiopsy specimens with the pattern of monoclonal secretion and the type of proteinuria and paraproteinuria. SUBJECTS AND METHODS: A study group comprised 25 patients with MM and severe RF; 22 of them underwent programmed hemodialysis. Immunochemical study of serum and urine proteins, renal puncture biopsy with light, immunofluorescence and electron microscopy examination of its specimens were performed in all the patients. RESULTS: Cast nephropathy (CN) is the most common type of renal impairment in patients with MM and severe RF. CN concurrent with monoclonal immunoglobulin deposition disease was identified in 32% of cases. In the mixed lesion, it is CN that is a determinant in the development of acute and chronic RF. Rare variants of nephropathies as fibrillary glomerulonephritis, immunotactoid nephropathy, and crystalline histiocytosis were found in 16% of cases. In most cases, severe RF in MM develops in case of low monoclonal secretion. However, there are a larger number of secreted and excreted monoclonal light chains in CN than in other variants of kidney lesion. Urinary paraprotein G excretion suggests that the glomerular filter is damaged. Degenerative changes in the podocytes and a reduction in their small processes were detected in the majority of cases. In glomerular or mixed proteinuria, there were also unorganized and organized deposits in the glomerular basement membrane. CONCLUSION: The pattern of nephropathy does not determine a renal response after chemotherapy. The reversibility of CN in MM depends on the magnitude of interstitial fibrosis and podocyte changes. The pronounced changes in the podocytes as a reduction in their small processes serves as a poor sign in achieving renal responses following chemotherapy.

[Crystalline histiocytosis].

The paper describes a case of diagnosis of the rare monoclonal secretion-associated disease crystalline histiocytosis with kidney and bone marrow involvement. The female patient with multiple myeloma (MM) was found to have intralysosomal crystals in the cells of the bone marrow (histiocytes, plasmocytes), kidneys proper (mesangiocytes, podocytes), and subsequently in those of a kidney graft. Lower secreted monoclonal IgG and ceased Bence-Jones protein secretion after MM chemotherapy were accompanied by improved and stabilized kidney graft function. However, a repeat morphological study of a renal biopsy specimen showed that the crystalline inclusions were preserved in the podocytes. By comparing the immunological and renal responses, it is reasonable to suggest that monoclonal IgG rather than Bence-Jones protein is of value in the pathogenesis of crystal formation.

[Nephropathy caused by non-amyloid organized and granular deposits as multiple myeloma syndrome].

A rare variant of nephropathy in multiple myeloma (MM) is reported. Nephropathy is characterized basing on the study of nephrobiopsy with light, immunofluorescent and electron microscopy. A repeat biopsy of the kidney was made after achievement of a complete clinicohematological remission. A MM patient's nephrobiopsy in a picture of glomerulonephritis had 3 types of deposits: granular, irregular fibrils of 12 nm in diameter and microtubes organized in bunches 19 nm in diameter. Congo red test was negative, cryoglobulinemia was absent. Immunofluorescent test detected deposit of monoclonal IgG in the mesangium and glomerular basal membrane (GBM) corresponding to monoclonal type of monoclonal secretion. After treatment and achievement of remission, neither IgG no light chains were found in nephrobiopsy. Electron microscopy registered complete resorption of granular deposits and microtubes with formation of electron-transparent cavities. However, fibrils seen before treatment only in mesangium appeared in the above hollow cavities. The presence of such fibrils in the mesangium and GBM did not influence clinical picture of the disease. After achievement of remission the patient had no clinical and laboratory signs of nephropathy, only insignificant selective glomerular proteinurea was observed (0,5 g/l). Thus, granular deposits and microtubes contained paraprotein, they were completely resorbed after achievement of MM remission. Fibrils seem to have another genesis unrelated to monoclonal gammapathy.

[Renal monoclonal immunoglobuline deposition disease as a rare variant of renal damage in multiple myeloma].

A case of the immunoglobuline deposit disease diagnosis in MM patient having the symptoms of intensive proteinuria, macrohematuria and terminal renal failure is reported. The disease was diagnosed by the evidence from electron microscopy of the kidney and liver biopsies.

[Immunotactoid glomerulonephritis].

Immunotactoid glomerulonephritis is a rare disease of unclear etiology and pathogenesis. Clinically immunotactoid glomerulonephritis manifests itself as the nephrotic syndrome in most cases. The diagnosis of the disease is based on electron microscopic findings and characterized by tubules, average 30 nm in diameter, aligned in parallel in the deposits of immune complexes. Light optic and immunohistochemical studies in this disease are not pivotal. Further investigation may reply to a number of questions at the formation of deposits of immune complexes and procedures of their elimination.

[Chronic heart failure in patients with cardiac amyloidosis].

Amyloidosis is a pathology caused by tissue deposition of amyloid, a compound composed of insoluble fibrillar proteins. AL-amyloidosis (primary amyloidosis) most frequently leads to cardiac disorders 50% of which are cases of chronic heart failure (CCF). The study was dictated by the rarity of this pathology among other causes of CCF, its severity, and poor prognosis in the absence of specific therapy. Cardiohemodynamics (CHD) and clinical course of CCF were examined in 12 patients with cardiac amyloidosis (CA) and clinical manifestations of CCF. All the patients died during the study period. The diagnosis was verified at autopsy in 5 patients, by gingival, rectal or pleural biopsy in 4, and from combination of clinical and instrumental findings in the remaining three. The longevity since the onset of CCF was 28 +/- 8.8 and 5.9 +/- 3.8 months in patients under and above 70 respectively. 83.3% of the patients with CA had suffered renal disorders (proteinuria, nephrotic syndrome, insufficiency) and loss of weight before they developed CCF. CCF concurrent with CA was characterized by severely disturbed systemic hemodynamics and refractivity to standard therapy. Cardiac disorders were dominated by changes in myocardium due to the substantial thickening of its walls. The weight of left ventricular myocardium was 358. 77 +/- 58.08g (by echoCG) and the total heart weight 552 +/- 98.4g (at autopsy). Patients with CCF and CA had CHD changes suggesting restrictive cardiomyopathy in 83.3% of the cases and dilatational cardiomyopathy in 16.7%.

[Arterial hypertension in chronic glomerulonephritis: detectability and treatment efficacy]. / Arterial'naia gipertoniia pri khronicheskom pri khronicheskom glomerulonefrite: chastota vyiavleniia i éffektivnost' lecheniia.

AIM: To study prevalence of arterial hypertension (AH) in patients with chronic glomerulonephritis (CGN), its relationship with activity of the renal process, renal function; to analyse policy and efficacy of antihypertensive therapy. MATERIAL AND METHODS A total of 250 CGN patients treated in 1993-2001 participated in the trial. They had different morphological variants of CGN. AH was diagnosed in 193 patients. In the course of the trial changes in antihypertensive treatment policy were observed. RESULTS: AH was most prevalent in mesangiocapillary (96.6%) and diffuse fibroplastic nephritis (83.9%). In functional insufficiency of the kidneys AH occurred in 90.1%. AH was associated with clinical and morphological signs of nephritis activity, severity of tubulointerstitial alterations, purin and lipid metabolism. Uric acid level and age were independent prognostic factors of AH development. AH correction was achieved in the initial and subsequent periods in 51.7 and 58.7% cases. Later, ACE inhibitors were prescribed more often, both in monotherapy and in combination with other drugs; calcium antagonists were taken less frequently. CONCLUSION: AH in CGN patients is a frequent finding and depends on a morphological nephritis variant, activity of the renal process and degree of renal failure. Age, gender and metabolic disorders are also involved in AH development in CGN patients. Recently, there is a trend to more frequent prescription of combined treatment. Drugs of choice in the treatment of renal AH are ACE inhibitors.

[The key role of tubulointerstitium remodeling in progression of chronic renal diseases]. / Kliuchevaia rol' remodelirovaniia tubulointerstitsiia v progressirovanii khronicheskikh zabolevanii pochek.

Tubulointerstitial fibrosis (TIF) is thought now to be a key factor in progression of renal failure in chronic nephropathies. A similar pattern of changes in glomerulonephritis and amyloidosis suggests common mechanisms operating in progression of renal failure in these nephropathies. Of importance in the process of interstitial inflammation is activation of the nuclear factor of transcription (NFkB) in tubular cells due to components of proteinuria and their secretion of some proinflammatory mediators, first of all chemokines with formation of inflammatory infiltrate and accumulation of interstitial myofibroblasts--the main source of extracellular matrix (ECM) components. Our findings are of interest in the light of current ideas that among ECM components the number of fibronectin deposites most of all reflects the severity of structural renal tissue damage including TIF and correlates with severity of renal failure.

[The role of viral infection in emergence and progression of primary glomerulonephritis and some nephropathies]. / Znachenie virusnoi infektsii v vozniknovenii i progressirovanii pervichnogo glomerulonefrita i nekotorykh nefropatii.

The results of this study confirm the importance of virus infection in nephropathy onset and progression. Virus-like inclusions were found at electron microscopy in 70 (46 children and 24 adults) of 136 total diagnostic biopsies. In another group of patients (68 adults--50 males and 18 females) with virus-like inclusions in the kidney biopsy studied electron microscopically detected 12 types of viruses observed by PCR in the tissue, present either separately or in various combinations, 2 or 3 simultaneously. The most widespread were Herpes simplex virus, adenovirus and hantovirus. Interrelationship between morphological forms of nephropathies and observed viruses is analyzed. Parvovirus B19 was observed only in FSGS/G and arteryohyalinosis.