Terapevticheskii arkhiv



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.



Irina Chazova
MD, PhD, Professor, Academician of the Russian academy of Sciences
ORCID: http://orcid.org/0000-0002-1576-4877



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



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Current Issue

Vol 95, No 6 (2023)

Cover Page

Full Issue


State-of-the-art paradigm of corticosteroid therapy for immune-mediated inflammatory kidney diseases
Bulanov N.M., Bobkova I.N., Moiseev S.V.

Since 1950’s corticosteroids (CS) have remained the cornerstone of immunosuppressive therapy for immune-mediated kidney diseases. However multiple adverse events, associated with the prolonged CS therapy, became the basis for the development of novel treatment approaches. Current evidence supports the implementation of the steroid-sparing regimens for the treatment of different types of glomerulonephritis. Randomised controlled trial PEXIVAS demonstrated the efficacy and safety of early steroid tapering, starting from the second week of therapy, in patients with ANCA-associated vasculitis with kidney involvement. Several trials showed the efficacy of oral prednisolone 0.3–0.5 mg/kg/daily as a part of multitarget therapy for severe proliferative lupus nephritis. A combination of calcineurin inhibitors and low-dose CS are effective for remission induction in membranous nephropathy, as well as the steroid-free rituximab regimen for the patients with moderate risk of disease progression. Medium dose CS showed promising effect in patients with IgA-nephropathy. Long-term high dose CS remain the standard-of-care for the treatment of minimal change disease and focal segmental glomerulosclerosis, however patients with steroid-dependent and relapsing disease tacrolimus and rituximab can help to achieve steroid-sparing effect. The role of CS pulse-therapy is currently debated, nevertheless it remains a compulsory treatment in several conditions. Thus, overall trend is directed towards the minimization of the maximal doses of CS and/or treatment duration. However, to implement this approach morphological verification of the diagnosis and personalized assessment of the potential risk and benefit are required.

Terapevticheskii arkhiv. 2023;95(6):451-456
pages 451-456 views

Original articles

Study of urinary markers of different podocytopathies by proteomic analysis
Vinogradov A.A., Chebotareva N.V., Bugrova A.E., Brzhozovskiy A.G., Krasnova T.N., Nasibullina K.Z., Kononikhin A.S., Moiseev S.V.

Background. Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays.

Aim. To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies.

Materials and methods. The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards.

Results. The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein.

Conclusion. Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

Terapevticheskii arkhiv. 2023;95(6):457-461
pages 457-461 views
Clinical significance of the determination of antibodies to thrombospondin type 1 containing domain 7A (THSD7A) in membranous nephropathy
Kakhsurueva P.A., Kamyshova E.S., Bobkova I.N., Stavrovskaya E.V., Rudenko T.E., Andreeva E.Y.

Background. Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN.

Aim. To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN.

Materials and methods. Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls.

Results. The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p>0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia).

Conclusion. THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

Terapevticheskii arkhiv. 2023;95(6):462-467
pages 462-467 views
Clinical significance of uremic toxin indoxyl sulfate and inflammation in the development of vascular calcification and cardiovascular complications in stage C3–C5D chronic kidney disease
Dzgoeva F.U., Remizov O.V., Goloeva V.G., Ikoeva Z.R.

Aim. To clarify the role of the uremic toxin indoxyl sulfate (IS) and inflammation in the development of vascular calcification and cardiovascular complications in chronic kidney disease (CKD).

Materials and methods. One hundred fifteen patients aged 25 to 68 years with CKD stage C3–C5D were examined. Serum concentrations of IS, interleukin 6 (IL-6), tumor necrosis factor (TNF-α), troponin I, parathyroid hormone were determined by enzyme immunoassay using kits from BluGene biotech (Shanghai, China), Cloud-Clone Corp. (USA), ELISA Kit (Biomedica, Austria).

Results. An increase in the serum concentration of IS, IL-6, TNF-α was revealed, which was significantly associated with a deterioration in renal function and changes in the morphological and functional parameters of the heart and aorta.

Conclusion. High concentrations of IS, IL-6, TNF-α, which are closely associated with an increase in renal failure and cardiovascular complications, indicate their significant role in vascular calcification, which underlies the damage to the cardiovascular system in CKD.

Terapevticheskii arkhiv. 2023;95(6):468-474
pages 468-474 views
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
Yurova V.A., Kozlovskaya N.L., Bobrova L.A., Kozlov L.V., Andina S.S., Demyanova K.A.

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.

Terapevticheskii arkhiv. 2023;95(6):475-480
pages 475-480 views
Prevalence, age and gender features of chronic kidney disease in patients with diabetes mellitus
Murkamilov I.T., Aitbaev K.A., Fomin V.V.

Aim. To study the prevalence, age and gender characteristics of chronic kidney disease (CKD) in patients with diabetes mellitus (DM).

Materials and methods. In a case-control study, clinical and laboratory data were analyzed in 683 patients with DM (4.6% of patients with type 1 DM and 95.4% with type 2 DM) and kidney damage. The indicators of anthropometry, hemodynamics and biochemistry were studied. The glomerular filtration rate (GFR) was calculated using the CKD-EPI formula.

Results. The proportion of middle-aged and elderly patients with CKD was the most numerous, amounting to 39 and 38%, respectively. At the same time, anemia was more common in young people, and hypercholesterolemia (35.0%), proteinuria (47.5%) and signs of renal failure (45.0%) – in middle-aged patients with CKD. 47.0% study participants had C1 and C2 categories of changes in renal function. Mean levels of systolic blood pressure (BP), the prevalence of proteinuria were statistically significantly higher in women. When evaluating the correlations, we found statistically significant relationships between the calculated GFR and the level of body mass index, systolic BP, venous blood glucose and Hb in the subgroup of men. Among females, a significant relationship between the calculated GFR value was revealed with indicators of systolic and diastolic BP, venous blood glucose and Hb concentration.

Conclusion. Our data indicate the existence of differences in the prevalence of CKD and associated risk factors for the progression of renal failure, depending on gender differences and living conditions of patients. In urban residents, CKD was most often associated with arterial hypertension and renal failure, while overweight, obesity, and proteinuria were significantly more common in rural areas. The incidence of proteinuria and mean levels of systolic BP were significantly higher in females. Further study of the issue under discussion seems promising from the standpoint of a personalized approach and the search for a new preventive strategy to combat both end-stage renal failure and its complications.

Terapevticheskii arkhiv. 2023;95(6):481-486
pages 481-486 views
Potential for infusion correction of COVID-19-associated endotheliopathy
Simutis I.S., Ratnikov V.A., Scheglov A.N., Nikolaeva O.V., Boyarinov G.A., Sapegin A.A., Gaikovaya L.B., Evteeva D.A., Zamyatina K.N.

Aim. To evaluate the relationship between the systemic inflammatory response and the severity of COVID-19-associated endotheliopathy and the effect of succinate-containing crystalloid solution (sodium meglumine succinate) on it in patients with severe COVID-19.

Materials and methods. Clinical and laboratory parameters of 53 intensive care unit's patients with COVID-19 complicated by community-acquired bilateral multisegmental pneumonia were analyzed. Intensive therapy complex of 27 patients (study group) included daily infusion of 1.5% solution of sodium meglumine succinate (Reamberin) in the daily dose of 10 ml/kg for at least 11 days (or during the whole stay in the unit). A similar volume of Ringer's solution was present in the control group of 26 patients. The levels of endotheliocytosis, homocysteine, and systemic inflammatory response were determined at all stages of the study.

Results. The evaluation of endotheliopathy degree in the meglumine succinate group showed a significant reduction of initially elevated levels of endotheliemia and homocysteinemia at all study stages. The pattern of changes in the study group was highly correlated (r=0.90–0.96) with the dynamics of systemic inflammatory response parameters-fibrinogenemia, C-reactive protein and interleukin-6 levels. As normalization of the immune imbalance, we regarded the termination of lymphopenia in the Reamberin group.

Conclusion. Early inclusion of Reamberin infusion into intensive therapy of severe COVID-19, in comparison with Ringer's solution, leads to significant and stable correction of the severity of systemic inflammatory response, which in turn is naturally reflected in the severity of endothelial dysfunction, multiple organ failure, and also leads to a decrease in 28-day mortality.

Terapevticheskii arkhiv. 2023;95(6):487-493
pages 487-493 views
Use of a combination of the virus-neutralizing monoclonal antibodies casirivimab and imdevimab for mild to moderate COVID-19 in patients at high risk of progression: Results of the non-interventional observational study
Lebedkina M.S., Fomina D.S., Mutovina Z.Y., Mаrkina U.A., Bogomolov P.O., Chulanov V.P., Lysenko M.A., Alexeeva E.I.

Aim. To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies – MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings.

Materials and methods. A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion.

Results. Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 – in 1.9% (n=2), by day 28 – in 0.9% of patients; to stay in the intensive care units by the 7th day – in 4.6% (n=5), by the 14th day – in 0.9% (n=1), by the 28th day – in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered.

Conclusion. An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

Terapevticheskii arkhiv. 2023;95(6):494-499
pages 494-499 views

Clinical notes

Nephrotic syndrome during pregnancy. Is it chronic glomerulonephritis or preeclampsia? Case report
Alekseeva M.V., Kozlovskaya N.L., Korotchaeva Y.V., Demyanova K.A., Chegodaeva A.G., Apresyan S.V.

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.

Terapevticheskii arkhiv. 2023;95(6):500-504
pages 500-504 views
Multisystem lesions in orphan diseases: rheumatological aspects of Fabry's disease. Case report
Mashkunova O.V., Isabekova A.H., Botabekova A.Z., Novikov P.I.

Fabry–Andersen disease is a genetically determined, progressive disease related to lysosomal storage diseases, linked to the X chromosome, characterized by impaired glycosphingolipid metabolism, due to the deficiency or absence of the enzyme α-galactosidase A. Fabry disease is a multisystem disease and is characterized by damage to vital organs – kidneys, heart, brain, with the occurrence of complications that cause an unfavorable prognosis. Autoinflammation mechanisms with signs of chronic inflammation are involved in the pathogenesis of the disease. One of the features of Fabry disease are clinical manifestations in the form of arthralgia, fever, skin lesions, which are similar to rheumatological diseases. The article presents a clinical observation of the classical type of Fabry disease with multiple organ manifestation, which required differential diagnosis with rheumatological diseases. Rheumatologists are specialists who are involved in the early diagnosis of Fabry disease, so they should have a high awareness of this sphingolipidosis.

Terapevticheskii arkhiv. 2023;95(6):505-510
pages 505-510 views
Various phenotypes of postpartum atypical hemolytic uremic syndrome: the role of genetic testing in determining prognosis. Case report
Kirsanova T.V., Balakireva A.I., Fedorova T.A., Pyregov A.V., Rogachevskiy O.V.

We report a case of atypical hemolytic uremic syndrome (aHUS) that occurred after childbirth in a patient with a history of numerous recurrent episodes of TMA with nephrotic proteinuria and impaired renal function. At 33 weeks of the first spontaneous pregnancy, proteinuria up to 0.8 g/l was first registered, at 38 weeks she was hospitalized with proteinuria, reaching a maximum of 13 g/l, she was delivered promptly, after which progressive thrombocytopenia was noted over the next few days (up to 44×109/l) and anemia and severe arterial hypertension, which could not be corrected by several groups of antihypertensive drugs. Initiated plasma therapy had no effect. After exclusion of all other causes of TMA, therapy with eculizumab was initiated, which made it possible to quickly and completely stop the phenomena of TMA. The presented observation demonstrates the successful treatment of recurrent course of aHUS with eculizumab with the achievement of complete recovery of kidney function in a patient with a homozygous mutation in the MCP gene. It is worth noting the importance of genetic research even in those situations where clinically aHUS is beyond doubt.

Terapevticheskii arkhiv. 2023;95(6):511-515
pages 511-515 views


Frailty and chronic kidney disease – the real problem of modern nephrology: A review
Rudenko T.E., Bobkova I.N., Kamyshova E.S., Stavrovskaya E.V.

The article deals with the syndrome of frailty or senile asthenia in patients with chronic kidney disease. The questions of prevalence, diagnosis, pathogenesis of this syndrome and its clinical consequences in chronic kidney disease are discussed.

Terapevticheskii arkhiv. 2023;95(6):516-520
pages 516-520 views

History of medicine

Cardiorenal syndromes: historical aspects and current challenges
Nezhdanov K.S., Milovanova L.Y., Strizhakov L.A., Krasnova T.N.

The article describes major milestones in acknowledgment of pathophysiological relationship between heart and kidneys since Ancient Egypt till our time and history of term “cardiorenal syndrome” (CRS). First references about kidney and heart functions could be dated to 13 BC when Hippocrates mentioned them. In the XIV century Gentile da Foligno proposed a hypothesis about functional interconnection between heart and kidneys. In the XVIII century Richard Bright described the link between myocardial hypertrophy and kidneys diseases. Frederic Justin Collet was the first one who used the term “cardiorenal” in his article in 1903. In Russia, I.I. Stolnikov conducted his experiments about myocardial hypertrophy and kidneys ischemia in 1880. Famous Russian internist, E.M. Tareev, devoted several paragraphs to cardiorenal interactions in his fundamental manuals “Anemia in Bright’s disease” (1929) and “Hypertension” (1948). The research on this topic was continued by Tareev’s followers: N.A. Mukhin, V.S. Moiseev, more recent successors – Zh.D. Kobalava, S.V. Moiseev, V.V. Fomin, S.V. Villevalde and others. Their contribution resulted in development of first Russian clinical guidelines on cardio and nephroprotection in CRS in 2014. In 2008 consensus of Acute Disease Quality Initiative summarized current experience on CRS. Today, research on controversial classification questions, biomarkers and other aspects of CRS continues.

Terapevticheskii arkhiv. 2023;95(6):521-525
pages 521-525 views

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