[Visceral leishmaniasis: a challenging diagnosis in internal medicine].

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.

[Glomerulopathy with fibrillary and tubular deposits].

The advent of up-to-date electron microscopes and molecular biological methods for the examination of renal puncture biopsies could define earlier undetectable and unworthy cellular structures and stromas. There is a diversity of diseases that can be diagnosed exclusively at the ultrastructural level, thus the literature has identified the concept of glomerular diseases with organized deposits. The current classifications based only on the ultrastructual deposits are imperfect as they fail to account for the etiological and pathogenetic features included in these diseases.

[Giant abdominal urate tumor-like mass with multiple crystalline deposits in the bowel and lung walls in a patent with terminal heart failure].

The paper describes a unique case of a large abdominal urate mass with a peculiar inflammatory process with giant cells and smaller urate deposits in the lung and small bowel without articular changes and kidney injury in a patient with terminal heart failure.

[Morphological verification of renal lesion as a compulsory stage in the diagnosis of Fabry disease].

The paper describes a case of Fabry disease in a patient in whom kidney biopsy enabled the renal lesion be characterized in detail. Fabry nephropathy-associated kidney tissue changes, including renal lesion, have been verified using electron microscopy of renal tissue.

[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.

[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.

[Fibrillary glomerulonephritis and immunotactoid nephropathy: the current view of the pathomorphological substrate of disease].

Fibrillary glomerulonephritis (FGN) and immunotactoid nephropathy (ITN) are diseases diagnosed only by electron microscopy. Until recently, information on the diseases has reached as reports on some cases. Much information, including the authors' observations, has been presently gathered so as there is a chance of attempting to pool and analyze it. It is quite obvious that investigators do not agree to evaluate FGN and ITN. Some authors are inclined to believe that these are one disease and propose to use the general term "fibrillary-immunotactoid nephropathy", we, like others, consider FGN and ITN as two different diseases. Our findings suggest that there are two diseases (FGN and ITN). We provide support for the data available in the literature on that the deposits are polyclonal in FGN and monoclonal in ITN. It is most likely that no sharp distinction can be made between FGN and ITN from the diameter of microtubules making up deposits (less or more than 30 nm); the procedure of their package and, to be sure, their chemical composition are of importance in establishing the diagnosis.

[Modification of direct immunofluorescence assay to study paraffin-embedded renal and skin tissue sections].

Immunofluorescence assay has been widely used so far to diagnose glomerular and some skin diseases. The optimal antigen persistence is achieved using the frozen sections; however, their considerable shortcoming is the impossibility to long store preparations and to use a morphology archive. Our laboratory has modified a direct immunofluorescence study on paraffin-embedded renal and skin tissue sections, substantially increasing its accessibility.

[Multiple myeloma in renal transplant recipients].

Severe renal failure (RF) may be the first and only clinical manifestation of multiple myeloma (MM). Occasionally the disease remains long unrecognized and the patients receive renal function replacement therapy, including renal transplantation (RT). To treat MM in renal transplant recipients is a complex medical and ethical problem. The paper presents the authors' experience in treating 3 patients with MM diagnosed after RT and evolving transplant lesion. Various morphological types of grafted kidney lesion were detected. These included fibrillar glomerulonephritis, cast nephropathy, and the latter concurrent with light-chain deposition disease. RF most rapidly progressed in cast nephropathy. The natural history of the disease was unfavorable in all patients; VAD and PAD chemotherapy programs proved to be ineffective. It is concluded that RT should not be performed in patients with extended-stage MM due to the fact that there is a considerable risk for renal transplant lesion and severe infectious complications that may occur during chemotherapy. Blood and urine immunochemical studies should be conducted in all the patients who are to undergo RT.

[Clinicomorphological characteristics of renal disorders in patients with genetic thrombophilia].

AIM: To characterize the course and clinicomorphological features of chronic glomerulonephritis (CGN) in patients with genetic thrombophilia. MATERIAL AND METHODS: A clinical picture and evidence on renal biopsy from 25 patients (12 females, mean age 32 +/- 12 years and 13 males, mean age 36 +/- 8.8 years) admitted to hospital with diagnosis of chronic glomerulonephritis were analysed. Mean duration of renal problem to the moment of biopsy was 37.6 +/- 39 months. Renal end point was stable rise of Scr > 1.4 mg/dl for 6 months. Polymerase chain reaction defined polymorphisms of the genes MTHFR C677T; PTG G20210A; FV Leiden G1691A; FGB G455A; ITGB3 T176C L33P; PAI-1 4G/5G 675. RESULTS: Mutation in one gene was detected in 24% patients, a multigenic form of thrombophilia--in 76% patients. Morphologically, all the patients' renal tissue had the signs of thrombotic microangiopathy (TMA), 8 patients had a combination of acute and chronic TMA. TMA was the only histological sign of nephropathy in 3 (13%) patients, the rest patients showed TMA combination with different morphological variants of CGN. Sclerotic alterations were most severe in combined carriage of the alleles 4G PAI-1 and T MTHFR. A correlation was found between the renal end point and number of mutant alleles (r = 0.6, p < 0.05), the presence of allele 4G (r = 0.46, p = 0.05) and interstitial sclerosis (r = 0.5, p = 0.05). CONCLUSION: Hereditary thrombophilia promotes induction of nephrosclerosis leading to activation of intraglomerular blood clotting which contributes to CGN progression. Patients with genetic thrombophilia may develop acute TMA as the only variant of renal damage.

[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%.

[Types of lupus nephritis exacerbations: prognostic significance].

AIM: To characterize the course of lupus nephritis (LN) in terms of demographic indices (sex, age of renal disease onset), the presence of antiphospholipid syndrome (APS) and to ascertain a prognostic role of the disease exacerbations. MATERIAL AND METHODS: A total of 121 LN patients were followed up from 1997 to 2004 (mean duration of the follow-up 5.6 +/- 6.4 years). A LN course was characterized by the presence of a complete or partial remission, exacerbation of the disease, repeated hospitalisations. Two types of exacerbations were considered: proteinuric, running with progressive proteinuria and normal renal function (type 1); functional, running with elevation of blood creatinine (type 2). RESULTS: Exacerbations were observed in one third of the examinees, 70% of them ran with renal dysfunction. Exacerbations occurred more frequently in males than in females (50 vs 27%, respectively; p = 0.08) and in patients with early onset of LN (at the age of 40 years and younger, 80 vs 60%, respectively; p < 0.05). Exacerbations of type 2 occurred in males, in patients with early onset of renal damage and in APS association. It is shown that LN exacerbations, their incidence and type (a functional type) have a negative influence on renal survival of the patients. CONCLUSION: Identification of groups of LN patients at high risk of exacerbations and unfavourable prognostic role of exacerbations dictates the necessity of due immunosuppressive therapy for maintenance of remission.

[Prostate-specific antigen and telomerase in prostatic cancers].

A correlation between the blood level of prostate-specific antigen (PSA) and the prostatic tissue activity of telomerase was analyzed in prostate cancer (PC), low- and high-grade prostatic intraepithelial neoplasia (LG PIN, HG PIN) and in benign prostatic hyperplasia (BPH). The study was based on the results of a comprehensive examination of 92 patients from the Clinic of Urology, I. M. Sechenov Moscow Medical Academy. 44% of the patients were diagnosed as having PC; 49% had LG PIN and BPH; 7% had HG PIN and BPH. Active telomerase in the prostate biopsy specimens was found in 98% of the patients with PC, in 33% of those with HG PIN, and in 20% of those with LG PIN. When active telomerase was detected in the prostate biopsy specimens of patients with urological cancer (PC, PIN, BPH, the blood content of total PSA) was statistically significantly higher than that in the absence of this enzyme.

[Fibrillary glomerulonephritis].

Fibrillary glomerulonephritis is a rare disease of unknown etiology and pathogenesis. In two thirds of cases, it is clinically manifested by the nephrotic syndrome resistant to cytostatic and corticosteroid therapy. Fibrillary glomerulonephritis is diagnosed by electronic microscopy and characterized by the presence of chaotically located fibrils with an average diameter of 18-22 nm in the deposits of immune complexes. Light optical and immunohistochemical studies are of no crucial importance in this disease. Further investigations may answer a number of questions as to the formation of immune complex deposits and ways of their elimination.

[Clinical implication of urine test for markers of endothelial dysfunction and angiogenesis factors in assessment of tubulointerstitial fibrosis in chronic glomerulonephritis].

AIM: To evaluate contribution of endothelial dysfunction and impairment of endothelial proliferation/ regeneration to mechanisms of development of tubulointerstitial fibrosis (TIF) in chronic glomerulonephritis (CGN) basing on urinary levels of markers of endothelial activation/impairment and angiogenesis factors. MATERIAL AND METHODS: A total of 67 CGN patients entered the study: 19 patients with moderate urinary syndrome (group 1), 37 patients with nephrotic syndrome (group 2), 11 patients with nephrotic syndrome and persistent renal failure (RF). A control group consisted of 12 healthy subjects. The examination covered excretion with urine of Willebrand factor (WF), plasminogen activator inhibitor I (PAL-I), fibrin degradation products (FDP), vascular endothelial growth factor (VEGF). These values were compared with severity of fibrous changes in renal interstitium estimated by biopsy morphometry. RESULTS: CGN patients had signs of affection of parietal effects of vascular endothelium. In particular, increased excretion of functionally active WF, PAI-I and FDP correlating with activity/severity of CGN. The changes were especially noticeable in patients with progressive forms of CGN (with NS and RF). Patients with morphologically verified TIF (interstitial area more than 20%) excretion of endothelial dysfunction markers was higher than in CGN patients free of TIF In a progressive course of nephritis endothelial dysfunction deteriorates by endothelial proliferation/regeneration impairment as shown by reduced urinary excretion of angiogenic factor VEGF and parallel elevation of functionally active WF in urine of patients with severe forms of CGN. Combined contribution of endothelial dysfunction and angiogenesis impairment to mechanisms of TIF development is seen from these values relations with severity of creatinemia and fibrous alterations in tubulointerstitial tissues of the kidney. CONCLUSION: The results point to participation of endothelium in mechanisms promoting development of TIF and RF in CGN both in terms of endothelial dysfunction and impairment of endothelial repair capacity. Clinicomorphological comparisons confirm the significance of WF, PAI-I and VEGF in assessment of local-renal endothelial changes and severity of fibrosis in renal tissue in CGN. Due to availability of the study material, perspectives of fibrogenesis monitoring in the kidneys with the tests appear which is essential for making prognosis and treatment policy in CGN patients.

[Clinicomorphological features of nephropathy in primary and secondary antiphospholipid syndrome].

AIM: To investigate specific features of extrarenal manifestations of antiphospholipid syndrome (APS) in patients with APS-associated nephropathy (APSN) in primary APS and lupus nephritis (LN) with secondary APS; to compare clinicomorphological signs of APSN in primary and secondary APS. MATERIAL AND METHODS: We examined 44 APSN patients with primary APS and 90 patients with LN: 57 with secondary APS, 33 with antiphospholipid antibodies (APA) without history of thrombosis. In addition to clinical and immunological examination, detection of serological APS markers, morphological examination of renal tissue and ultrasound dopplerography (USDG) of the renal vessels were made (in some patients) for assessment of the condition of intrarenal vascular bed. RESULTS: In patients with primary APS, renal disorder and secondary APS in LN frequency of arterial thrombosis doubles that of venous ones. Renal disorder irrespective of a clinical APS form (primary, secondary) combines with affection of the CNS, heart and skin (livedo). This correlates with frequency of arterial thrombosis. In patients with primary APSN rate of arterial hypertension (AH), especially severe, and renal dysfunction is higher than in LN with APS while this group is characterized by more severe proteinuria, microhematuria and higher incidence of nephrotic syndrome. A direct correlation exists between the incidence of arterial thrombosis and severity of AH, between AH and renal ischemia by USDG. Morphologically, glomerulosclerosis, marked arteriolosclerosis and diffuse interstitial sclerosis occur more often in patients with primary APSN compared to LN patients with APS. CONCLUSION: In primary and secondary (in SLE) APS combination of APSN with impairment of the CNS, heart and skin, correlation of its basic clinical manifestations with arterial thrombosis allow us to single out a special clinical variant of APS manifesting with generalized ischemic lesions of the organs as a result of arterial/arteriolar thrombosis. Irrespective of its nature, APSN has common characteristic features--combination of AH, persistent renal dysfunction and transitory hypercreatininemia--correlating with development of arterial thrombosis; therefore, this pathology can be considered as a variant of thrombotic vascular lesion of the kidneys.

[Independent postmortem examination: contents of its concept, organizational aspects of its performance].

The paper discloses the contents of the concept of independent postmortem examination and describes the organizational aspects of postmortem examination according to the materials of primary postmortem studies of autopsy and biopsy of surgically removed organs.

[Urine excretion of a monocytic chemotaxic protein-1 and a transforming growth factor beta1 as an indicator of chronic glomerulonephritis progression].

AIM: To measure urine and renal tissue levels of profibrogenic mediators (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF-b1) in patients with chronic glomerulonephritis (CGN); to specify significance of these mediators for assessment of inflammation and fibrosis in the kidney and as prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue, interstitial area, respectively, in 63 patients with active proteinuric CGN. RESULTS: Patients with active proteinuric forms of CGN have higher urine excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in patients with nephrotic syndrome was significantly higher than in patients with moderate urinary syndrome. The highest MCP-1 urine excretion was observed in patients with persistent renal failure. Urine excretion of TGF-b1 depended on the level of creatinemia being the highest in marked proteinuria and stable renal dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with expression of this cytokine in renal interstitium. This confirms its local-renal origin. A correlation was found between urine values of MCP-1, TGF-b1 and severity of tubulo-interstitial fibrosis (TIF). High informative value (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time shown as markers of interstitial fibrosis. They are also important for making prognosis of CGN. CONCLUSION: It is shown that MCP-1 and TGF-b1 are essential for remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used as criteria of activity and prognosis of CGN.