Terapevticheskii arkhiv

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Monthly peer-review medical journal

 

Editor-in-Chief

Irina Chazova
MD, PhD, Professor, Academician of the Russian academy of Sciences
ORCID: 0000-0002-1576-4877

 

About

Therapeutic archive journal (ISSN key title is "Terapevticheskiy arkhiv") was founded by the prominent Russian therapists M.P. Konchalovsky and G.F. Lang in 1923. Then its editors-in-chief were Professors V.N. Vinogradov and A.G. Gukasyan. Since 1972, E.I. Chazov, Academician of the Russian Academy of Sciences, has been heading the editorial board of the journal.

Over 90 years, there have been more than 1000 issues where the authors and editorial staff have done their best for readers to keep abreast of current advances in medical science and practice and for physicians to master the advanced principles of recognition and treatment of a wide spectrum of visceral diseases.

The papers published in the journal (editorials, original articles, lectures, reviews, etc.) cover both current scientific achievements and practical experience in diagnosing, treating, and preventing visceral diseases. The authors of publications are not only Russian, but also foreign scientists and physicians. All papers are peer-reviewed by highly qualified Russian specialists.

The journal is published monthly. Traditionally, each issue has predominantly certain thematic areas covering individual therapy specializations. Every year, one of the issues is devoted to related problems in practical medicine (allergology and immunology, neurology and psychiatry, obstetrics, oncology, etc.). This all draws the attention of the reading public to the journal.

 

Publications

Monthly issues publish in print and online in Open Access under the Creative Commons NC-ND 4.0 International Licensee.


 

Indexation

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    • Russian Science Citation Index (RSCI)
    • Core Collection (Science Citation Index Expanded)
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  • Index Medicus
  • Current Contents Connect
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  • Ulrich’s Periodicals Directory
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Current Issue

Vol 96, No 6 (2024)

Cover Page

Full Issue

Editorial

Kidney involvement in rare hereditary diseases
Moiseev S.V., Shilov E.M.
Abstract

Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant and benign tumors. Genetic nephropathy should be always considered in children, adolescents and young patients with the kidneys or urinary tract disorders and/or patients with positive family anamnesis. Extrarenal manifestations can be a valuable clue for diagnosis of certain hereditary diseases, e.g. neurosensory deafness in Alport syndrome or photofobia in nephropathic cystinosis. Diagnosis of monogenic inherited diseases should be verified by genetic testing. Specific drugs are available for treatment of certain hereditary diseases involving kidney, e.g. Fabry disease, cystinosis, primary hyperoxaluria I type and atypical hemolytic uremic syndrome.

Terapevticheskii arkhiv. 2024;96(6):559-564
pages 559-564 views

Original articles

Comparison of thrombodynamic methods and routine hemostasis tests in the evaluation of hypercoagulable syndrome in chronic glomerulonephritis
Chebotareva N.V., Kharionovskaya E.A., Biryukova E.A., Berns S.A., Vuimo T.A.
Abstract

Background. Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients.

Aim. To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN).

Materials and methods. The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed.

Results. Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained.

Conclusion. In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.

Terapevticheskii arkhiv. 2024;96(6):565-570
pages 565-570 views
Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension
Akaeva M.I., Kozlovskaya N.L., Bobrova L.A., Vorobyeva O.A., Stoliarevich E.S., Shatalov P.A., Smirnova T.V., Anan'eva A.O.
Abstract

Background. The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy.

Aim. To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH.

Materials and methods. 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome – exome) by next-generation sequencing technology (NGS).

Results. GD of CS were detected in a quarter of patients. Rare genetic variants classified as “likely pathogenic” including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3).

Conclusion. Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy.

Terapevticheskii arkhiv. 2024;96(6):571-579
pages 571-579 views
Idiopathic membranous nephropathy with focal segmental sclerosis
Kamyshova E.S., Bobkova I.N., Kakhsurueva P.А., Abdulaeva A.S., Rudenko T.Е., Stavrovskaya E.V., Andreeva E.Y., Li O.А., Suvorov A.Y.
Abstract

Aim. To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients.

Materials and methods. 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months.

Results. At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio – OR 1.12, 95% confidence interval – CI 1.03–1.22; р=0.07), FSGS (OR 0.05, 95% CI 0.01–0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12–0.95; р=0.039) were associated with the CKD progression.

Conclusion. In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.

Terapevticheskii arkhiv. 2024;96(6):580-586
pages 580-586 views
Clinical and morphological correlations in patients with lupus nephritis: a retrospective study
Kurginian K.V., Stoliarevich E.S., Litvinova M.A., Kokhanchuk V.A., Shevchenko S.N., Pugach V.A., Novikov P.I., Moiseev S.V., Bulanov N.M.
Abstract

Aim. To analyze associations between clinical and morphological features of kidney involvement in patients with systemic lupus erythematosus.

Materials and methods. In the retrospective cohort study, we enrolled adult (≥18 years) patients with morphologically proven lupus nephritis (LN) stratified according to the ISN/RPS classification. Systemic lupus erythematosus was classified in accordance with ACR/EULAR classification criteria (2019). Antiphospholipid syndrome was diagnosed according to the 2006 classification criteria. Disease activity was assessed with SELENA-SLEDAI score.

Results. We enrolled 62 patients with LN, among them 84% were females. Median age of SLE onset was 23 (16,3; 30,8) years. In all cases kidney involvement was accompanied by extrarenal manifestations, among which joint (82%), skin (57%) and hematological involvement (68%) was the most common. LN class I was proven in one patient, class II – in three patients, class III – in 24, including III+V in seven, class IV – in 18, including IV+V in two, class V – in 13, class VI – in three patients. APS nephropathy was diagnosed in 4 (6.5%) of patients with LN. The most common clinical manifestation was proteinuria (85%), however its prevalence, level and the frequency of nephrotic syndrome showed no significant differences between the LN classes. LN III/IV±V was characterized by the highest levels of serum creatinine (and the lowest eGFR) at the time of biopsy.

Conclusion. LN is characterized by the high heterogeneity of the clinical and morphological manifestations, which makes LN class prediction impossible without kidney biopsy.

Terapevticheskii arkhiv. 2024;96(6):587-592
pages 587-592 views
End products of glycation (AGEs) and inflammation in the clinic of cardiovascular complications and vascular calcification at different stages of chronic kidney disease (G1–G5D)
Fatima D.U., Remizov O.V., Ikoeva Z.R., Tedeeva I.V., Gusalov A.A., Goloeva V.G.
Abstract

Aim. To clarify the role of advanced glycation end products (AGEs) and inflammation in the development of vascular calcification and cardiovascular complications at different stages of chronic kidney disease (CKD) G1–G5D.

Materials and methods. We examined 105 patients aged 19 to 75 years with stage C1–C5D CKD, 77 (74%) of whom were patients with diabetic nephropathy. The concentration of AGEs, interleukin (IL)-1, IL-6 and tumor necrosis factor α (TNF-α), troponin I, parathyroid hormone was determined by enzyme-linked immunosorbent assay (ELISA) using kits from BluGene biotech (Shanghai, China), Cloud-Clone Corp. (USA), ELISA Kit (Biomedica, Austria).

Results. A high content of AGEs, IL-1, IL-6, TNF-α was established, which directly correlated with the increase in renal failure and changes in the morpho-functional parameters of the left ventricle and aorta.

Conclusion. An increase in serum concentrations of AGEs and inflammatory mediators, correlating with a decrease in renal function and changes in the morpho- functional parameters of the left ventricle and aorta, indicate their significant role in the processes of damage to the cardiovascular system in CKD.

Terapevticheskii arkhiv. 2024;96(6):593-599
pages 593-599 views
Immunosuppression, tonsillectomy and remissions in high-risk IgA-nephropathy
Kochoyan Z.S., Lieva A.Z., Galkovskaya T.O., Dobronravov V.A.
Abstract

Aim.To evaluate the efficacy of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with high-risk IgA nephropathy (IgAN).

Materials and мethods. The retrospective study cohort included cases with primary IgAN (n=213, age 34±11 years, male 52%) at high risk of progression with clinical and morphological data collected. The follow-up was 26 (10; 61) months. The association of IST without TE (IST; n=141) or with TE (IST+TE; n=72) with the development of complete (PR), partial (PR) and overall (PR or PR, OR) remissions was investigated.

Results. The incidence of achieving early PR or OR in the IST and IST+TE groups was 65.2% and 86.1%, respectively (p=0.002). The probability of early PR or OR was significantly increased in the IST+TE group compared to IST [HR 1.714 (1.214–2.420) and HR 3.410 (1.309–8.880), respectively]. IST+TE was associated with a 3- to 4-fold increase in the likelihood of PR or OR at the end of follow-up [HR 2.575 (1.679–3.950) and HR 4.768 (2.434–9.337), respectively]. Analyses using pseudorandomisation methods yielded similar results.

Conclusion. TE may be effective for remission induction in high-risk IgAN.

Terapevticheskii arkhiv. 2024;96(6):600-605
pages 600-605 views
Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis
Markina M.V., Milovanova L.Y., Lysenko L.V., Milovanova S.Y., Volkov A.V., Beketov V.D., Lebedeva M.V., Nezhdanov K.S., Moiseev S.V.
Abstract

Aim. To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС).

Materials and methods. Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 – GN with ANCA-associated systemic vasculitis, 20 – GN with systemic lupus erythematosus (SLE) at early (all I–II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer).

Results. The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors – the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3–4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved.

Conclusion. Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Terapevticheskii arkhiv. 2024;96(6):606-613
pages 606-613 views
New medical technologies in cough therapy: results of a double-blind randomized placebo-controlled multicenter clinical trial
Polyakova E.A., Ushakova S.E., Okovityy S.V., Zaytsev A.A., Bagaeva M.I.
Abstract

Aim. To study the efficacy and safety of Eladis® in comparison with placebo in patients with non-productive cough.

Materials and methods. A phase III clinical trial enrolled 250 patients aged 18–65 years with acute respiratory viral infection with upper respiratory tract involvement or acute bronchitis. Patients were randomized into 2 groups of 125 subjects: group 1 received Eladis® (40 mg tablets), group 2 received a matching placebo. The patients received the study drugs 1 tablet BID for 7–14 days. After the treatment, patients were followed up (day 7±2) to assess the effect of therapy on the frequency of coughing attacks, the frequency and severity of daytime and nocturnal cough, the severity of cough, the duration of clinical cough cure, and the effect on the severity of the main acute respiratory viral infection symptoms.

Results and conclusion. The results of the study demonstrate the overall efficacy and statistically significant superiority of Eladis® over placebo: there were significant differences between the study groups in the proportion of patients who decreased the coughing attack frequency by ≥50% by day 5 (p<0.0001). In addition, the clinical cure of cough in the Eladis® group occurred 2 days earlier: the median time was 6 days, vs 8 days in placebo group. There was a decrease in the frequency of cough attacks and a decrease in its severity by more than 3.5 points by day 5 of treatment. All the effects were associated with high safety of the drug.

Terapevticheskii arkhiv. 2024;96(6):614-621
pages 614-621 views

Clinical notes

Challenges in diagnosing familial Mediterranean fever: exploring atypical clinical features. Clinical case
Barsuk M.V., Novikov A.V., Mikhalina T.A., Rameev V.V., Lysenko L.V.
Abstract

This clinical case series presents descriptions of 3 patients with familial Mediterranean fever (FMF) who have atypical manifestations and abnormal inheritance mechanisms in terms of Gregor Mendel's laws. Although molecular genetic testing can help with disease diagnosis, it is not always conclusive. The primary need for genetic testing in atypical cases is to explain the mechanism of inflammation and to select the optimal therapy. These clinical observations demonstrate the changes in the spectrum of phenotypic manifestations of FMF in the context of the widespread introduction of molecular genetic methods.

Terapevticheskii arkhiv. 2024;96(6):622-627
pages 622-627 views

Reviews

Lupus nephritis and thrombotic microangiopathy: A review
Bobrova L.A., Kozlovskaya N.L.
Abstract

Lupus nephritis (LN) is one of the most common organ-specific manifestations of systemic lupus erythematosus (SLE). Various clinical signs of LN develop in at least 50% of patients with SLE. In addition to LN, the spectrum of renal lesions associated with SLE also includes vascular pathology. One of the variants of renal microvascular injury is thrombotic microangiopathy (TMA), the mechanisms of which are diverse. The review focuses on the main forms of TMA, including antiphospholipid syndrome and nephropathy associated with antiphospholipid syndrome, TMA caused by complement system regulation disorders and deficiency of ADAMTS13. In most cases, these forms of TMA are combined with LN. However, they may also exist as a single form of kidney damage. This article discusses the TMA pathogenesis, the impact on kidney prognosis, and treatment options.

Terapevticheskii arkhiv. 2024;96(6):628-634
pages 628-634 views

History of medicine

History of the study of amyloidosis: from the Rokitansky’s theory to the present day
Rameev V.V., Lysenko L.V.
Abstract

In the history of amyloidosis studying the concept of liquids dyscrasia has been predominated and finally it is resulted in accepting a serum protein-precursor as a leading amyloidogenic factor in the disease pathogenesis. Consequently basic diagnostic and treatment strategy was aimed to find and eliminate this protein from the blood and this approach evidenced high effectiveness in most frequent AA and AL-amyloidosis characterized with anomaly high levels of precursors in the blood. At the same time there are less frequent and slower progressing inheritant forms of systemic amyloidosis including transthyretin induced, which are less depending on amyloidogenecity of amyloid precursor and because of that, in example, the effectiveness of transthyretin stabilizers or blockers of its synthesis is limited comparing with the precursor elimination in AA or AL. Developed in the middle of XX century a theory of local synthesis by macrophages is more preferable to describe the pathogenesis of these forms. And modern proteome analysis using give rise to confirm the key meaning of macrophage in the amyloidogenesis and proves necessity to know deeply mechanisms of macrophagial autophagia – basic tool of maintaining intracellular protein homeostasis. That is why it is difficult to hope on high effectiveness of chemical amyloid solvents in vivo, which being under macrophages regulation never could realize its chemical activities.

Terapevticheskii arkhiv. 2024;96(6):635-640
pages 635-640 views


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