Vol 95, No 6 (2023)

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.

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.

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.

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.

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.

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.

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.

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.

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.