[Comparative characteristics of the complement system in patients with C3-glomerulopathy and atypical hemolytic uremic syndrome of chronic course who suffered an acute episode of thrombotic microangiopathy].

AIM: To compare changes in the complement system in C3-glomerulopathy (C3-GP) and atypical hemolytic uremic syndrome (aHUS) after the relief of an acute episode of thrombotic microangiopathy. MATERIALS AND METHODS: The study included 8 patients diagnosed with C3-GP and 8 with aHUS in remission. The blood levels of the complement system components were determined: C3, C4, C3a, C5a, factor H (CFH), factor B (CFB), membrane-attacking complex (MAC), antibodies to C3b (anti-C3b-AT), the level of hemolytic activity (CH50), the content of factor D (CFD) in the urine. RESULTS: C3 and CH50 levels were within the reference range in both groups, however, in the C3-GP group they were at the lower limit, and C3 level was significantly lower than in the aHUS group: 0.56 [0.44; 0.96] vs 1.37 [1.16; 2.52] (p=0.003). CFB increased level was detected in both groups, but in the C3-GP group it was significantly lower than in the aHUS group - 275.1 [222.1; 356.6] vs 438.7 [323.3; 449.3] (p=0.010). C3a, C5a and MAC levels were increased in both groups, but the maximum was in the C3-GP group, and the MAC level in the C3-GP group was 2 times higher than that in aHUS, and these differences reached statistical significance - 123 555±6686 vs 5603±1294 (p=0.036). CFH and CFD levels was increased in both groups, but their highest values was in the aHUS group. CONCLUSION: Alternative complement pathway activation signs were present in both groups of patients with complement-mediated nephropathies, regardless the stage of the disease. In C3-GP, alternative complement pathway activation was more pronounced than in aHUS after the relief of an acute episode of thrombotic microangiopathy.

[Nephrotic syndrome during pregnancy. Is it chronic glomerulonephritis or preeclampsia? Case report].

Nephrotic syndrome (NS) during pregnancy is a fairly rare pathology and its descriptions in the literature are few. For a long time, NS was associated only with an exacerbation of chronic glomerulonephritis or de novo nephritis, however, the experience of recent years has shown that NS can be a manifestation of the classical obstetric pathology - preeclampsia (PE). The appearance of massive proteinuria with the development of NS is most typical for early PE, which, of course, makes diagnosis difficult, especially if PE develops at an unusually early time (up to 20 weeks). To describe PE that does not fit into the classical criteria, the term "atypical" PE is now used, the development of which can be promoted by both obstetric and somatic risk factors. The presented clinical observation describes the development of early (within 14 weeks) severe PE with the NS at the onset of the disease in a patient with the first multiple pregnancy and complete hydatidiform mole (HM) of one of the fetuses. The progression of nephropathy with the addition of thrombotic microangiopathy and HELLP syndrome made it possible to assume the diagnosis of PE with a high probability. The rapid relief of all clinical manifestations after delivery confirmed this assumption. The role of HM as the main trigger of unusually early PE is discussed. Apparently, the patient's trophoblast disease in the form of hydatidiform mole caused the formation of a severe angiogenic imbalance already in the early stages of pregnancy, which led to the development of PE, which manifested NS as a consequence of podocytopathy due to VEGF deficiency. Thus, the development of NS in a pregnant patient without a history of kidney disease dictates, first of all, the exclusion of PE, until proven otherwise.

[Analysis of the course and outcomes of pregnancy in patients with advanced stages chronic kidney disease].

BACKGROUND: Pregnancy in patients with advanced chronic kidney disease (CKD) is associated with a high risk of adverse outcomes for the mother and the fetus, but data on the characteristics of the course of pregnancy in these women is limited. AIM: To analyse of the course and outcomes of pregnancy in patients with CKD stages 3a4. MATERIALS AND METHODS: Thirty five pregnant women with CKD stages 34 were included: 3a 12 (34.3%) patients, stage 3b 10 (28.6%), stage 4 13 (37.1%). RESULTS: Proteinuria, serum creatinine, blood pressure in dynamics, the presence of a physiological response were investigated. Pregnancy management included blood pressure correction, antianemic, antiplatelet, anticoagulant therapy, prevention and treatment of urinary infection, correction of metabolic disorders. All pregnant women had proteinuria of varying severity, which increased towards the end of pregnancy. Seventeen (51.5%) patients had hypertension, successfully corrected with antihypertensive drugs. The average delivery term was 34.6 weeks. Preeclampsia developed in 14 (42.4%) cases, an inverse relationship was found between the presence of a physiological response and preeclampsia (p=0.009; rs=-0.463). All children were born alive and viable. After delivery in patients with CKD 3a creatinine values returned to the pre-gestational level, in patients with grade 3b and 4 progression of CKD was noted. CONCLUSION: A favorable pregnancy outcome in women with late stages of CKD is possible with constant monitoring by a multidisciplinary team of doctors with mandatory monitoring of renal function, proteinuria, blood pressure, coagulation, markers of preeclampsia and indicators of fetal health. It was proposed to consider the physiological response of the kidneys to pregnancy as a predictor of a favorable outcome.

[Changes in the complement system in membranoproliferative glomerulonephritis]. / Izmeneniia v sisteme komplementa pri membranoproliferativnom glomerulonefrite.

AIM: To compare the clinical manifestations membranoproliferative glomerulonephritis (MPGN) in its idiopathic variant, lupus nephritis (LN), and C3 glomerulopathy (C3-GP), by comparing them with changes in the complement system. SUBJECTS AND METHODS: The clinic of nephrology followed up 42 patients with different types of MPGN in 2013 to 2015. The study included 35 patients divided into 3 groups: 1) 8 patients with C3-GP, 2) 13 with idiopathic MPGN; 3) 14 with Class IV LN. The investigators studied the blood and urine levels of components and markers for activation of the classical and alternative pathways (C3 and C4, С3а, C5a, CFH, CFB, and CFD) of the terminal complement complex (TCC). RESULTS: The detection rate of C3-GP was 19%. The patients with C3-GP were noted to have the lowest blood concentration of S3 and the highest urinary level of С3а, C5a, TCC, CFH, CFB, and CFD. C3 nephritic factor was detected in 2 patients from the C3-GP (dense deposit disease) group. CONCLUSION: Alternative complement pathway dysregulation caused by genetic or autoimmune factors plays a leading role in the pathogenesis of C3-GP.

[Complement System Abnormalities in Patients with Atypical Hemolytic Uremic Syndrome and Catastrophic Antiphospholipid Syndrome].

Background: The role of the alternative complement pathway (AP) abnormalities in the pathogenesis of aHUS is well studied. Clinical and morphological manifestations of atypical HUS and catastrophic APS are often similar. However, studies on the state of AP in patients with CAPS are virtually absent. Aims: The aim of our study was to assess the state of AP in patients with CAPS and aHUS. Patients and methods: The study enrolled 67 patients (pts) with a diagnosis of CAPS (28 pts) and aHUS (39 pts). Studies of the complement system are made of 10 pts with CAPS and 20 aHUS. Factor H, I, B, D content, functional activity of factor H, and complement components C3, C4 was determined in serum by ELISA kit. Results: Patients with CAPS and aHUS showed similar changes in complement biomarkers. The factor H level in the serum was significantly higher than the standard value. However, the specific activity of factor H reduced, mean rate 59% for aHUS and 26% for CAPS. The median value of factor D was twice higher than the normal range in both groups, indicating the activation of the AP. Conclusions: There are indications of an AP activation not only in pts with aHUS but in CAPS pts too. We suppose that the activity of factor H is a more sensitive indicator of complement system changes than factor H level. Patients with CAPS and aHUS have similar clinical and laboratory characteristics. However, CAPS is more severe, with the involvement of a larger number of vascular beds. Perhaps this is due to the double damaging effects on the endothelium ­ of antiphospholipid antibodies (aPL) and activated complement. So we hypothesize that CAPS can be called aPL-mediated TMA in pts with a complement system defect.

[Incomplete thrombotic microangiopathy as a variant of hemolytic-uremic syndrome].

The described case illustrates difficulties in diagnosing atypical hemolytic-uremic syndrome (aHUS) in incomplete thrombotic microangiopathy (TMA) in the absence of thrombocytopenia, one of the signs of the classic triad of aHUS, which has resulted in the delayed verification of its diagnosis and in progressive kidney injury. The paper discusses the need to carry out kidney biopsy and to include sHUS in both the presence of a complete set of symptoms of this disease and in the absence of one of them into a range of diagnostic search.

[Cardiac involvement in thrombotic microangiopathies].

AIM: To describe cardiac involvement in patients with acute thrombotic microangiopathy (TMA). MATERIALS AND METHODS: The case histories of 46 patients with proven TMA, including 17 patients diagnosed with atypical hemolytic uremic syndrome (aHUS) and 29 patients with catastrophic antiphospholipid syndrome (CAPS), were analyzed. RESULTS: Different documentarily verified signs of cardiac involvement were revealed in 6 (13%) patients (5 and 1 patients diagnosed as having aHUS and CAPS, respectively). Five patients developed myocardial involvement at disease onset in the presence of multiple organ dysfunction. CONCLUSION: Cases of cardiac involvement in TMA of various genesis are presented. The exact incidence of myocardial involvement and its prognostic value are unknown so far.