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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 eGFR30% 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 (Exp=6.4, 95% confidence interval CI 1.429.3; p=0.017). Early remission was associated with the presence of remission at the end of follow-up (Exp=6.3, 95% CI 2.218.4; p=0.001). Specific treatment (Exp=0.308, 95% CI 0.1080.881; p=0.028) and late remission (Exp=0.079, 95% CI 0.0170.368; 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.

Aim. То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST). Materials and methods. An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30). Results. In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups. Conclusion. The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

Aim. An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). Materials and methods. A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). Results. All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. Conclusion. IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.

ABSTRACT Objective The aim of this randomized comparative study was to assess renal and metabolic effects of vildagliptin in insulin-treated type 2 diabetes (T2DM) patients without overt chronic kidney disease. Subjects and methods We randomized 47 insulin-treated non-proteinuric patients with satisfactory controlled T2DM and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 either to continue insulin therapy (control) or to receive combined insulin-vildagliptin treatment (VIG group). We assessed eGFR using serum creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys), and urinary creatinine-adjusted excretion of albumin (UACR), type IV collagen (uCol IV/Cr), and neutrophil gelatinase-associated lipocalin (uNGAL/Cr) at baseline and after 6 months of treatment. Results Study groups were comparable in terms of age and sex (60.1 ± 6.1 years and 42.9% men in control group vs. 60.8 ± 5.2 years and 39.1% in VIG group). After 6 months of treatment, there were no significant changes in main assessed parameters in control group. VIG group demonstrated significant decrease in HbA1c, diastolic blood pressure, frequency of hypoglycemia, and high-sensitivity C-reactive protein level as compared to the changes in control group. While eGFRcreat, UACR, and uNGAL/Cr showed no significant changes after vildagliptin addition, eGFRcys, eGFRcreat-cys, and uCol IV/Cr changed significantly in comparison with control group (+7.0% [3.7;13.3]; +5.1% [1.4;8.5]; -32,8% [-55.8;-24.4], respectively, p < 0.01 each). Correlation and regression analysis revealed glucose-independent pattern of these changes. Conclusion Addition of vildagliptin to ongoing insulin therapy in patients with T2DM was associated with a reduction in uCol IV/Cr and an increase in eGFRcys and eGFRcreat-cys, independent of T2DM control parameters.

Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity. Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p