Vol 94, No 6 (2022)

Cover Page

Full Issue


Lupus nephritis in the XXI century

Bobkova I.N., Moiseev S.V., Lysenko L.V., Kamyshova E.S.


Lupus nephritis (LN) is the most common organ lesion in systemic lupus erythematosus (SLE), developing in 40–50% of patients. Due to immunosuppressive therapy, the survival of patients with SLE has increased significantly over the past 50 years, and the proportion of severe kidney damage in the death structure has decreased. However, LN relapses and complications of immunosuppression, accelerated atherogenesis, concomitant diseases lead to the accumulation of organ damage and an increased risk of death. The article consideres the place of kidney damage in the SLE, the risk factors for LN development, the main renal histopathological changes, it identifies a number of issues that need to be addressed to optimize treatment and improve LN long-term outcomes, including, the revision of pathogenetic therapy regimens with restriction of glucocorticosteroids and prescribing drugs with steroid-sparing activity, the integration of new drugs for LN treatment, wider use of modern nephroprotection capabilities.

Terapevticheskii arkhiv. 2022;94(6):713-717
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Original articles

Remissions and progression of C3 glomerulopathy

Karunnaya A.V., Dobronravov V.A.


Aim. To analyze the outcomes of C3-glomerulopathy (C3-GP) and determine the associated factors.

Materials and methods. A retrospective single-center study included 60 patients with newly diagnosed C3-GP (with primary C3-GP – pC3-GP – 82%). Of these, 48 (80%) patients had clinical data to assess the following disease outcomes: development of remission and disease progression (by a composite endpoint that included initiation of chronic dialysis or a decrease in estimated glomerular filtration rate – eGFR – <15 mL/min/1.73 m2 or a decrease in eGFR≥30% of baseline at the time of renal biopsy). The median follow-up period was 25 (7; 52) months.

Results. At early follow-up (median 4 [3; 9] months) remission was registered in 35% of patients; at the end of follow-up, in 48% (for pC3-GP, 32 and 41%). Disease progression occurred in 17 patients. In the overall group the likelihood of achieving early remission was higher with treatment (Expβ=6.4, 95% confidence interval – CI 1.4–29.3; p=0.017). Early remission was associated with the presence of remission at the end of follow-up (Expβ=6.3, 95% CI 2.2–18.4; p=0.001). Specific treatment (Expβ=0.308, 95% CI 0.108–0.881; p=0.028) and late remission (Expβ=0.079, 95% CI 0.017–0.368; p=0.001) were associated with reduced risk of disease progression in multivariable models (adjusted for eGFR, mean blood pressure). The same results were obtained for the group of patients with pC3-GP.

Conclusion. C3-GP is a variant of severe complement-mediated glomerular damage with unfavorable renal prognosis, which requires timely personalized expert-level diagnostics with clarification of etiopathogenesis of the disease followed by therapy aimed at achieving remission to improve outcomes.

Terapevticheskii arkhiv. 2022;94(6):718-724
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Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs

Grechukhina K.S., Chebotareva N.V., Zhukova L.G., Androsova T.V., Karpov V.V., Krasnova T.N.


Background. Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy.

Aim. To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs.

Materials and methods. The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1α (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters.

Results. A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1α and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1α in urine during the first two weeks of therapy.

Conclusion. The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1α in urine during the first two weeks after the start of therapy.

Terapevticheskii arkhiv. 2022;94(6):725-730
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Clinical significance of serum levels of osteoproteherin and sclerostin in assessment of vascular calcification in chronic kidney disease stage 3–5

Dzgoeva F.U., Remizov O.V., Botcieva V.K., Goloeva V.G., Malakhova N.G., Ikoeva Z.R.


Aim. To clarify the mechanisms of the effect of osteoprotegerin (OPG) and sclerostin on vascular calcification and the state of the cardiovascular system in chronic kidney disease (CKD).

Materials and methods. A total of 110 patients aged 18 to 65 years with CKD stages 3–5D were examined. OPG, sclerostin, intact parathyroid hormone, and serum troponin I were determined using the commercial "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" from Cloude-Clone Corp. (USA) by enzyme-linked immunosorbent assay.

Results. An increase in sclerostin and OPG levels was revealed, which significantly correlated with a decrease in glomerular filtration rate, as well as an increase in left ventricle myocardial mass index and peak systolic blood flow in the aortic arch.

Conclusion. Changes in the regulation of bone-mineral metabolism, in which the proteins inhibitors of bone metabolism, OPG and sclerostin, as well as the interactive interaction between the vascular and skeletal systems, play a decisive role in the development of lesions of the cardiovascular system caused by vascular calcification in CKD.

Terapevticheskii arkhiv. 2022;94(6):731-737
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Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome

Berns A.S., Sovetnikov E.N., Chebotareva N.V., Berns S.A., Solonkina A.D., Guliaev S.V., Kraeva V.V., Moiseev S.V.


Background. Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance.

Aim. Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS.

Materials and methods. The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT.

Results. According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway.

Conclusion. In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

Terapevticheskii arkhiv. 2022;94(6):738-742
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Risk factors of kidney injury in patients with COVID-19

Shchepalina A.A., Chebotareva N.V., Kitbalian A.A., Potapov P.P., Nartova A.A., Akulkina L.A., Brovko M.Y., Sholomova V.I., Moiseev S.V.


Aim. To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19.

Materials and methods. We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans.

Results. AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI – 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression.

Conclusion. The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.

Terapevticheskii arkhiv. 2022;94(6):743-747
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New opportunities for neuroprotective therapy of patients in the acute and early recovery period of ischemic stroke

Tanashyan M.M., Raskurazhev A.A., Zaslavskaya K.I., Kuznetsova P.I., Merkulova I.Y.


Aim. To evaluate the efficacy and safety of Brainmax® in comparison with ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate in patients with ischemic stroke in the acute and early recovery period.

Materials and methods. An open multicenter randomized study included 180 patients aged 18–80 years (mean age 60.91±7.66 years, men 47.8%) with ischemic stroke in the acute and early recovery period (NIHSS from 3 to 15 points). Patients were randomized to receive Brainmax®, ethylmethylhydroxypyridine succinate and trimethylhydrazinium propionate in an equal ratio (n=60). The drugs were administered intravenously for 10 days, followed by a transition to intramuscular injection for 14 days. Efficacy was assessed using the following scales: Modified Rankin Scale, NIHSS, Rivermead Mobility Index, Montreal Cognitive Assessment Scale (MoCA). Safety assessment was carried out according to the presence and structure of adverse events.

Results. The mean Modified Rankin Scale score for Visits 3 (day 10) and 5 (day 25) for the group treated with Brainmax® was 2.41±0.85 and 1.44±0.91 points, for the group EMHPS – 2.87±0.68 and 2.18±0.85 points, and for the group receiving trimethylhydrazinium propionate – 2.87±0.50 and 2.55±0.70 points respectively, which reflects the best functional outcome in the Brainmax® group (p<0.05). Comparison of cognitive function indicators also showed statistically significant differences between the groups of drugs Brainmax® and ethylmethylhydroxypyridine succinate. Evaluation according to the MoCA test showed that the use of Brainmax® is 20% more effective in restoring cognitive functions (compared to monodrugs).

Conclusion. The present study confirms the superiority of combination therapy with Brainmax® over monotherapy with each of the components.

Terapevticheskii arkhiv. 2022;94(6):748-755
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Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B–4 stages of chronic kidney disease: prospective, randomized, controlled clinical study

Milovanova L.Y., Taranova M.V., Volkov A.V., Milovanova S.Y., Beketov V.D.


Background. It has been established that the use of a low-protein diet (LPD) in combination with ketoanalogues (KA) of essential amino acids can contribute to cardio- and nephroprotection in chronic kidney disease (CKD). Moreover, it has been shown that replacing part of the animal protein with soy protein (SP) in the diet contributed to more pronounced nephro- and cardioprotection in CKD, however, the data, available in the literature, are mainly represented by experimental studies.

Aim. To compare the effects of 2 types of diets on the main parameters of nephro- and cardioprotection in patients with CKD.

Materials and methods. We have conducted a prospective, randomized, controlled clinical study which included 85 patients with 3B–4 stages of CKD, compliant to LPD (0.6 g of protein/kg body weight) + KA (1 tablet/5 kg body weight). 43 patients (Group 1) received LPD with replacing animal protein with soy (60% soy protein + 40% another vegetable proteins) + KA, and 42 patients (control group, Group 2) received LPD (60% animal protein + 40% vegetable protein) + KA, within 12 months.

Results. The dietary substitution of animal protein with SP to a greater extent delayed the decrease in glomerular filtration rate (-5.9% vs -13.3%; p=0.048), the increase in left ventricular hypertrophy (+4.7% vs +12.3%; p=0.042), as well as the increase in central systolic blood pressure (+2.6% vs +13.0%; p=0.021), augmentation index (+7.6% vs +23.3%; p=0.010), slowed down the decrease in lean body mass in men (+0.9% vs -11.2%; p=0.017) and women (-1.8% vs -10.3%; p=0.024), increase in phosphorus (-10.3% vs +13.0%; p=0.029), cholesterol (-10.7% vs -3.4%; p=0.047) and urea (+6.3% vs +19.6%; p=0.035) serum levels.

Conclusion. The use of LPD with substitution of animal protein with soy protein + KA provides a more pronounced effect on nephro- and cardioprotection as well as maintenance of nutritional status, than conventional LPD + KA in patients with 3B–4 stages of CKD.

Terapevticheskii arkhiv. 2022;94(6):756-762
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Impact of kidney biopsy on the management of patients in the rheumatology department: retrospective study

Kokhanchuk V.A., Skvortsov A.V., Shchegoleva E.M., Kuznetsova E.I., Novikov P.I., Stoliarevich E.S., Varshavsky V.A., Moiseev S.V., Bulanov N.M.


Background. Kidney involvement is a common manifestation of the systemic autoimmune rheumatic diseases. Kidney biopsy is the “gold standard” for the diagnosis of kidney diseases, however this method has not yet become the standard-of-care in rheumatology practice.

Aim. To assess the diagnostic value of kidney biopsy in the management of patients of the rheumatology department.

Materials and methods. In this retrospective observational study we analyzed the medical documentation including kidney morphology findings in the patients of the Department of Rheumatology at Tareev Clinic of Internal Diseases. All patients included in the research had signs of kidney involvement and had undergone needle biopsy of the kidney or re-evaluation of the kidney tissue received previously.

Results. From June 2016 to October 2021, 3110 patients were admitted to the rheumatology department. Among them 63 (2%) underwent kidney biopsy and were included in the study. Twenty (32%) were male. Mean age was 42.5±13.9 years. The most common preliminary diagnoses before kidney biopsy were ANCA-associated vasculitis (n=17), systemic lupus erythematosus (n=12), and AA-amyloidosis associated with inflammatory joint diseases (n=7). In 14 (27%) patients diagnosis was unspecified at the time of biopsy. Among 49 patients with established preliminary diagnosis morphological findings were in line 38 (78%) with the pre-liminary diagnosis. However, in 11 (22%) patients morphological findings resulted in the change of the diagnosis. In all 14 patients with unspecified condition kidney biopsy helped to establish clinical diagnosis. Ultrasound evaluation demonstrated hematoma formation in 18 (31%) patients, and among them two required blood component transfusions.

Conclusion. Our study demonstrates significant value and safety of kidney biopsy in the patients with autoimmune rheumatic conditions. We suggest that kidney biopsy should be implemented in the management of this category of patients.

Terapevticheskii arkhiv. 2022;94(6):763-768
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Clinical notes

Diagnostic and treatment difficulties in kidney damage in the patient with generalized sarcoidosis during COVID-19. Case report

Lebedeva M.V., Chebotareva N.V., Beketov V.D.


The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.

Terapevticheskii arkhiv. 2022;94(6):769-771
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Modern view on the complement system role in membranous nephropathy

Kamyshova E.S., Semeryuk T.A., Bobkova I.N.


Membranous nephropathy (MN), an immune-mediated glomerular disease, is the most common cause of adult nephrotic syndrome. In MN, proteinuria is developed by podocyte damage due to the complement system activation in response to the subepithelial deposition of immune complexes containing various auto- and exogenous antigens. Membrane-attacking complex (MAC) is the terminal product of any complement pathways activation (classical, lectin or alternative) and plays the leading role in the complement-mediated podocytic damage. Thus far, the main pathway of complement activation leading to the formation of MAC in MN has not been established. The review highlights current evidence of various complement pathways activation in the development of MN, as well as recently established new molecular mechanisms of complement-mediated podocyte damage.

Terapevticheskii arkhiv. 2022;94(6):772-776
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History of medicine

Kidney damage caused by lead exposure: historical aspects

Arkhipov E.V., Garipova R.V., Strizhakov L.A., Bobkova I.N., Tairova N.


The article presents an historical analysis of publications devoted lead intoxication to kidney damage developing during contact with lead. It is shown that one of the manifestations of occupational intoxication with this metal can be toxic nephropathy.

Terapevticheskii arkhiv. 2022;94(6):777-780
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On the history of specialization in the clinic of internal diseases: the role of S.S. Zimnitsky (Kazan) in the formation of nephrology in the USSR

Borodulin V.I., Banzelyuk E.N., Topolyanskiy A.V.


Russian nephrology, like most clinical disciplines, has passed through two stages in its historical development: at the first stage, it became isolated as an important area of scientific research within the framework of the Soviet clinic of internal diseases, at the second stage it became an independent scientific and educational clinical discipline and medical specialty. The article shows the role of Kazan internist S.S. Zimnitsky as one of the founders of nephrology in the USSR at the first stage of its formation and as one of the leaders of the functional direction in Soviet clinical medicine.

Terapevticheskii arkhiv. 2022;94(6):781-785
pages 781-785 views

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