[Left ventricular noncompaction concurrent with bronchoectatic disease complicated by secondary AA-amyloidosis with renal involvement].

The paper describes a clinical case of congenital cardiomyopathy (left ventricular noncompaction) concurrent with secondary amyloidosis and renal involvement that develops at the outcome of long existing brochoectatic disease.

[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.

[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.

[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.

[Clinical and morphological characteristics of lupus nephritis in systemic lupus erythematosus with antiphospholipid syndrome].

AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical picture, urine indices were examined in 138 patients with SLE, APS and renal dysfunction. RESULTS: LN associated with APS is characterized with marked arterial hypertension, such patients had arterial thromboses more frequently than patients with isolated LN. Patients with anticardiolipin antibodies have arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal impairment in SLE may run not only with LN but also with thrombotic microangiopathy modifying clinical symptoms and course of the disease.

[Clinical significance of myocardial lesion in antiphospholipid syndrome].

Antiphospholipin syndrome (APLS) is one of the most frequent reasons for arterial and venous thromboses. Primary and secondary APLS can lead to thrombotic process in coronary arteries. The biggest diagnostic difficulties appear in cases of small coronary vasal involvement leading to diffuse myocardial lesion. Perfusion myocardial scintigraphy (MS) allows specification of the character of myocardial changes. Revealing of myocardial changes by means of MS makes it possible to start timely anticoagulative therapy, which significantly improves prognosis and life quality.

[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.

[Clinical manifestations of APS-nephropathy in primary antiphospholipid syndrome]. / Klinicheskie proiavleniia nefropatii, sviazannoi s antifosfolipidnym sindromom, pri pervichnom antifosfolipidnom sindrome.

AIM: To elicit clinical features of nephropathy associated with antiphospholipid syndrome (APSN) in patients with primary antiphospholipid syndrome (PAPS). MATERIAL AND METHODS: The analysis of clinical characteristics and course of APSN has covered 24 patients with PAPS (16 females and 8 males, mean age 34.3 years). Renal damage was represented by arterial hypertension (AH), urinary syndrome, functional decline. All the patients were tested for anticardiolipin antibodies and/or lupus anticoagulant. Renal biopsy was made in 7 patients. RESULTS: PAPS patients developed renal affection in the onset of APS or within the first 5 years of its course. In the majority of patients APSN combined with abnormalities of CNS, heart and skin. Arterial/arteriolar thromboses prevailed. APSN manifested with: AH (n = 23, severe AH in 11), abnormal renal filtration (n = 17, creatinine rise in 8), urinary syndrome with proteinuria (n = 23, in 14 with hematuria). The following clinical variants of APSN were proposed: urinary syndrome with AH (n = 16; 67%), acute nephritic syndrome (n = 7; 29%), nephrotic syndrome (n = 1). Morphological studies of biopsies from APSN patients have revealed sclerotic changes, thrombotic microangiopathy, nonspecific alterations in the glomeruli. CONCLUSION: APSN is a variant of microvascular renal affection caused by thrombotic processes in intra-organ microcirculation. It is an early clinical marker of APS. Clinically, APSN manifests with vascular renal affection, the earliest symptom being inhibition of glomerular filtration. Clinical combinations of the symptoms allow to distinguish variant of APSN suggesting the existence of acute and chronic APSN. Combination of APSN with affection of the CNS, heart and skin points to a special PAPS subtype characterized by generalized ischemic damage to the organs as a result of intraorganic arterial and/or arteriolar thromboses.

[Role of ultrasound dopplerography with acute captopril test in assessment of renal hemodynamics in chronic glomerulonephritis]. / Pol' ul'trazvukovoi dopplerografii s ispol'zovaniem ostroi farmakologicheskoi proby s kaptoprilom v otsenke pochechnoi gemodinamiki pri khronicheskom glomerulonefrite.

AIM: To examine blood flow in renal and intrarenal arteries and its changes in the acute pharmacological test with captopril in patients with chronic glomerulonephritis (CGN). MATERIAL AND METHODS: Renal circulation was studied in 50 patients with CGN using ultrasound dopplerography (USDG) of renal vessels on the unit GE Logiq 400 CL PRO Series. The velocity and indices of peripheral blood resistance in the major renal artery (RA) and in intrarenal arteries were estimated. In 26 patients the blood flow was studied again after intake of 50 mg captopril. RESULTS: Poor renal blood flow was registered in cortical parenchyma in 36% CGN patients (with chronic renal failure in 75%). Multifactorial regression analysis has demonstrated that only blood creatinine was independently related with slowing down of the blood flow at the level of RA and intrarenal arteries. Morphological index of activity correlated with resistance indices while a high sclerosis index correlated with blood flow slowing. Older patients had higher resistance indices. Captopril significantly accelerated blood flow and insignificantly changed indices of peripheral resistance including those in CRF patients. CONCLUSION: Poor blood flow in the cortical layer of renal parenchyma in CGN, according to USDG, occurs rather frequently and was associated with CRF and older age of the patients. Blocking of renin-angiotensin system at the level of angiotensin II formation improves renal blood flow in most of the patients.

[The course and prognosis of mesangioproliferative glomerulonephritis]. / Techenie i prognoz mezangioproliferativnogo nefrita.

AIM: A retrospective analysis of a clinical course of mesangioproliferative glomerulonephritis (MPGN) in patients with glomerular deposition of IgA (IgA nephropathy--IgA-N), with glomerular deposition of other Ig to determine prognostic factors of MpGN progression including IgA-N and to examine the patients' sensitivity to immunodepressive therapy. MATERIAL AND METHODS: 2000 patients with primary MPGN followed up from 1980 to 1999 from the disease onset to development of chronic renal failure (creatinine > 2.5 mg%). Factors affecting kidney survival were studied using the Cox regression model, factors predicting sensitivity to immunodepressive therapy--using multiple logistic regression. RESULTS: IgA-N differed by the course and prognosis from other forms of MPGN. In IgA-N urinary syndrome and macrohematuria were encountered more frequently, in other forms of MPGN more frequent was nephrotic syndrome. Prognosis of patients with IgA-N was worse than in MPGN patients without IgA deposition: 10-year "renal survival" (creatinine < 2.5 mg%) was 64 and 97% (p < 0.05), respectively. Prognosis-deteriorating factors for MPGN patients were the following: male sex, nephritis onset in 40-year-olds and older subjects, acute nephritic syndrome (creatinine > 1.5 mg%), high proteinuria, hematuria (> 50 in sight), the presence of synechia and TIC in renal biopsy, location of immune deposits both in the mesangium and basal glomerular membranes. The responders to the immunodepressive therapy had 10-year renal survival 100%. Positive results of immunodepressive therapy were observed significantly more frequently in patients with normal level of creatinine, moderate hematuria, absence of synechias and TIC in renal biopsy, given large total course dose of corticosteroids and cytostatics. Efficiency of oral cyclophosphamide and its intravenous pulse-therapy did not differ significantly. In pulse therapy an average cumulative dose was lower 6 times, side effects occurred 3 times less frequently. CONCLUSION: The importance of morphological information for prognosis and predicting sensitivity of MPGN patients to immunosuppressive therapy necessitates renal biopsy before therapy. Intravenous pulse therapy with cyclophosphamide is preferable as an active treatment in patients with sclerosis in renal biopsy.

[Use of angiotensin-converting enzyme inhibitors in chronic kidney insufficiency]. / Primenenie ingibitorov angiotenzinprevrashchaiushchego fermenta pri khronicheskoi pochechnoi nedostatochnosti.

AIM: To study effects of ACE inhibitors in patients with diffuse renal diseases at the stage of chronic renal failure (CRF). MATERIAL AND METHODS: Acute changes in renal filtration and in renal hemodynamics in response to 100-200 mg captopril were studied in 7 patients with CRF and 6 patients with intact renal function. Effects of long-term ACE inhibitors were retrospectively studied in 50 patients with CRF (27 men, 23 women, mean age 46.0 +/- 1.9 years, 7 patients were over 60 years old). Sixteen patients were selected from this group who were followed up for a long time. They were examined for CRF progression rate when given conventional antihypertensive treatment and after treatment with ACE inhibitors. RESULTS: Acute response to ACE inhibitors was the following: SCF fell by 18.4% on the average by the end on therapy week 1; by the end of week 3 renal hemodynamics showed stability, SCF returned to normal, effective renal plasm flow rose by 16.9%, serum potassium rose significantly after 7 days of treatment but did not reach 6 mmol/l. Effects of long-term ACE inhibitor in CRF: the treatment was discontinued after 30-60 days in 12 of 50 patients because of high creatinine (> 20%); in 38 patients ACE inhibitor had a pronounced antihypertensive and antiproteinuric action for 2-3 years, creatinine growth inhibited. Progression of CRF became slow. CONCLUSION: ACE-inhibitors in CRF had a nephroprotective effect but blood creatinine levels should be controlled especially within the first 1-2 months of treatment.

[Kidney damage in primary antiphospholipid syndrome]. / Porazhenie pochek pri pervichnom antifosfolipidnom sindrome.

AIM: To characterize clinical manifestations, course and laboratory signs of nephropathy in primary antiphospholipid syndrome (PAS). MATERIAL AND METHODS: 6 patients with PAS and renal affection were observed for 10 years since 1991. They were examined for anticardiolipin antibodies and/or lupus anticoagulant. Renal tissue was studied morphologically in one patient. RESULTS: In all the patients renal damage manifested with arterial hypertension associated with isolated proteinuria. The majority of the patients had renal dysfunction. All of them had elevated level of antibodies to cardiolipin primarily in combination with lupus anticoagulant. Histological changes of renal tissue presented with thrombotic microangiopathy of glomerular and extraglomerular vessels, intimal proliferation and vascular wall thickening with occlusion of their lumen which combined with morphological indicators of focal segmental glomerulosclerosis. CONCLUSION: The thrombotic process in the intrarenal vessels in PAS dictates the necessity to develop novel approaches to treatment of such patients. In addition to immunodepressants the treatment should include indirect anticoagulants and antiaggregants.

[Experience in the use of valsartan with the aim to inhibit progression of kidney failure in patients with chronic glomerulonephritis]. / Opyt primeneniia valsartana s tsel'iu tormozheniia progressirovaniia pochechnoi nedostatochnosti u bol'nykh khronicheskim glomerulonefritom.

AIM: To assess the effect of valsartan, angiotensin-II receptor blocker type 1, on key factors of progression of chronic renal failure (CRF)--arterial hypertension (AH), proteinuria (PU), sodium excretion (SE)--in patients with chronic glomerulonephritis (CGN) and initial affection of renal function. MATERIAL AND METHODS: 11 patients (mean age 33.7 +/- 13.3 years, mean duration of nephritis 8.6 +/- 6.4 years, male to female ratio 8:3) with AH (AP > 140/90 mm Hg) and marked PU (> 1 g/day) who had not received immunosuppressive drugs for at least 6 months before the trial were given valsartan. It was administered after the period of "washing out" at the initial dose 80 mg/day with further addition of diuretics or raising the dose twice (in hyperuricemia) to decrease AP under 140/90 mm Hg. The duration of the treatment was 3 months. RESULTS: After 3 months of valsartan therapy systolic arterial pressure fell from 162 +/- 18 to 138 +/- 20 mm Hg (p < 0.05), diastolic pressure from 100 +/- 8 to 92 +/- 15 mm Hg (single measurements). 24-h monitoring of AP showed a significant lowering of mean 24-h and night systolic and diastolic AP, day-time diastolic AP, 24-h time index of systolic and diastolic AP. Initial antiproteinuric effect was observed after 1 month of the treatment and after 3 months of therapy PU reduced significantly (from 5.7 +/- 6.0 g/day to 3.3 +/- 3.3 g/day). After 3 months sodium excretion significantly rose, while creatinine level and glomerular filtration rate did not. Potassium rose in one patient. CONCLUSION: In CGN with initial CRF valsartan in a dose 80-160 mg/day produces a pronounced antihypertensive and antiproteinuric actions, stimulates sodium excretion. No serious side effects were noted. It is necessary to continue studies on the ability of valsartan to inhibit progression of CRF.

[Primary focal segmental glomerulosclerosis: clinical and morphological prognostic factors]. / Pervichnyi fokal'no-segmentarnyi glomeruloskleroz: klinicheskie i morfologicheskie faktory prognoza.

AIM: To retrospectively analyze clinical course and results of immunodepressive therapy of patients with primary focal-segmental glomerulosclerosis (FSGS), to reveal prognostic factors of the disease progression and patients' sensitivity to immunosuppressive therapy. MATERIAL AND METHODS: Morphological diagnosis was specified, morphological indices of activity and sclerosis were estimated, renal survival was analysed, mono- and multivariate analysis of prognostic factors was made by the evidence obtained in the study of 135 biopsy specimens from CRF patients meeting the criteria of FSGS. RESULTS: At the moment of the disease onset only age of the patients was related to FSGS: 5- and 10-year survival was 100% if the disease started under 16 years of age, if older--the survival was 80 and 65%, respectively. Nephrotic syndrome, hematuria, high creatinine, racemose alterations in the glomeruli worsened the disease prognosis. When cytostatics and corticosteroids were used in combination they produced better results and were associated with better prognosis than each of them in monotherapy. Patients with marked hematuria and low proteinuria were less sensitive to therapy than those with weak hematuria and high proteinemia. Patients with FSGS having high IA and SI required more aggressive therapy for response. CONCLUSION: Renal biopsy with quantitation of IA and IS increases the prognosis accuracy and is important for choice of the treatment policy in patients with primary FSGS.

[Lupus nephritis and pregnancy]. / Volchanochnyi nefrit i beremennost'.

AIM: To evaluate effects of pregnancy on the course and prognosis of lupus nephritis and fetal outcome, in particular, in patients with lupus nephritis (LN) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A retrospective analysis was made of the course of LN in 31 females (44 pregnancies). RESULTS: A favorable outcome of pregnancy is possible in LN women if they had a persistent remission at conception. However, one third of these women had exacerbations of LN in pregnancy and early postpartum period. Pregnancy developing in active LN aggravated LN course in all the women. Fetal outcome was unfavorable. LN was especially severe if it arose in the course of pregnancy or early postpartum period. It seems that the presence of APS affected pregnancy outcome in a less degree than LN activity. CONCLUSION: Both in pregnancy and postpartum period, LN showed frequent exacerbations, but if the conception takes place during a persistent remission of LN, under adequate care and treatment, a delivery of a viable child is possible without an extraordinary risk for the mother.

[Urinary fibronectin as an indicator of kidney fibrosis in nephritis]. / Fibronektin mochi kak pokazatel' protsessov fibrozirovaniia v pochke pri nefrite.

AIM: To investigate clinicomorphological relationships between elevated urinary excretion of fibronectin (FN) and development of fibrosis in the kidney in patients with lupus nephritis (LN) and chronic glomerulonephritis (CGN). MATERIALS AND METHODS: Urinary FN excretion was measured at radial immunodiffusion in 54 LN patients. Of them, 15 patients had inactive LN, 39 patients had active LN varying in clinical forms. Urinary FN was also measured by passive hemagglutination in 36 CGN patients (11 inactive CGN and 25 active CGN cases). Biopsy specimens were obtained from 49 patients with active nephritis (43 with CGN and 6 with LN). FN deposits were studied immunohistochemically and morphometrically with determination of relative fibrosis area. RESULTS: Urinary FN excretion in patients with nephritis was higher than in healthy controls. In active CGN and LN the levels of FN were significantly higher than in inactive CGN and LN. The highest FN urinary concentrations were registered in patients with severe CGN and LN, especially in the presence of renal failure and arterial hypertension. Among them, the highest individual values were observed in patients with rapidly progressive nephritis. No positive correlations were found between the degree of the urinary FN excretion increment and degree of proteinuria. This suggests local-renal origin of most urinary FN. Morphologically, FN deposits were revealed in 73% of the biopsies. In most of the patients with severe nephritis both in CGN and LN there was a diffuse distribution of FN in the glomerules and interstitium. A correlation with a morphological nephritis type was absent, but existed between FN presence in the renal biopsies and relative area of interstitium (fibrosis). CONCLUSION: FN excreted in high amounts with urine in nephritis originates from the kidneys and reflects severity of fibrogenesis in the kidney.