[Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data].

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

[Immunological monitoring of the efficacy of extracorporeal photopheresis for prevention of kidney transplant rejection].

BACKGROUND: The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology. AIM: To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation. MATERIALS AND METHODS: A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated. RESULTS: Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04). CONCLUSION: ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period. BACKGROUND: The concept of the formation of immunological tolerance is a promising direction for correcting the renal transplant rejection. One of these methods is extracorporeal photochemotherapy (ECP), however, according to the literature, there is no single concept of its mechanisms of action in the formation of immunological tolerance in transplantology. AIM: To assess the effect of the preventive use of extracorporeal photochemotherapy on the factors of cellular immunity that contribute to the development of long-term tolerance in patients after kidney transplantation. MATERIALS AND METHODS: A total of 24 patients after a cadaveric kidney transplantation with group matching were included in the study. During the first six months after transplantation, 15 patients of the main group (MG) underwent 10 sessions of ECP in combination with the standard immunosuppression protocol, and 9 patients of the control group (CG) received only standard immunosuppressive therapy. Immunological studies were carried out by the 3rd year after transplantation. The number of cells expressing the antigens CD3, CD4, CD8, CD19, CD16 and CD56, the expression of co-stimulating molecules CD25, CD28 on T-lymphocytes, the number of T-regulatory cells with the CD3+ CD4+ CD25+ (hi) CD127- phenotype was evaluated. RESULTS: Compared with early post-transplant period, the number of naive CD3+CD4+CD45RO-CD28+ T-cells and CD28+ antigen expression was not different between two groups by 3 years after transplantation and with a group of otherwise healthy individuals (p=0.47 and p=0.26, respectively). Three years after transplantation, the T-helper lymphocyte count (CD3+CD4+) in MG were significantly higher than in CG (48.5+/-7.3% vs. 43.0+/-4.6%, respectively; p=0,04), cytotoxic T-lymphocytes count (CD3+CD8+) was 29.5+/-8.9% in MG, compared to 36.1+/-8.6% in CG (p=0.09), the ratio of CD4+/CD8+ in MG was significantly higher (1.83+/-0.72) than in CG (1.29+/-0.49) (p=0.04). CD19+ lymphocytes count was significantly below normal values in both groups, but in the CG it was more pronounced than in the MG (5.06+/-2.1% and 7.73+/-3%, respectively, (p=0.02) In the long-term period, CD3+CD4+CD25+(hi)CD127- T-regulatory cells count in MG was significantly higher than in CG (20.6+/-10.76*106/L and 12.9+/-4.97*106/l, respectively) (p=0.04). CONCLUSION: ECP initiates immunological tolerance through the activation of a second co-activation pathway between B-7 and CTLA-4 molecules in the early period after kidney transplantation. As a result, a clone of tolerogenic CD3+CD4+ T-lymphocytes is formed, which differentiates into T-regulatory cells and maintains immunological tolerance in the long-term period. Using ECP as a part of combination therapy allows to normalize the indicators of cellular immunity in the long-term period.

The state of the immune system in abdominal sepsis.

AIM: To evaluate the prognostic value of cytokine profile, phagocytosis activity indices, endotoxin concentration and activity in blood in gram-negative sepsis. MATERIALS AND METHODS: 78 patients with abdominal sepsis were included in a one-center prospective cohort study, of them 45 died. All the patients were evaluated for the concentration of circulating cytokines (TNF-α, IFN-γ, IL-6, IL-8, IL-10), cellular molecules (CD3, CD45RO, CD95 and HLA-DR), bactericidal and phagocytic activity of neutrophils and endotoxin (lipopolysaccharide) level in peripheral blood. RESULTS: The concentrations of all cytokines were slightly lower in the survivors. Significant differences were noted for TNF-α (p=0.001), IL-6 (p=0.001), and IL-8 (p=0.007). The expression of HLA-DR molecules was slightly higher (p=0.055), and CD95 was lower (p=0.146) in survivors than in the dead. However, the differences have not reached the required level of statistical significance. The phagocytic (p<0.001) and bactericidal activity (р=0.002 for stimulated activity and p=0.001 for spontaneous activity) of neutrophils is significantly different. In survived patients, we noted large values of stimulated bactericidal activity and phagocytic index than the dead. Level of spontaneous activity in survivors was lower. In subsequently deceased patients, the level of endotoxin load was higher than in the surviving patients: level of lipopolysaccharide concentration (p=0.002), endotoxin activity (p=0.032) and neutrophils activity (p=0.028). CONCLUSION: Evaluation of cytokine levels is informative, but due to the high spread of indicators in different patients, should be carried out in the dynamics. The most informative prognostic parameters in sepsis are the concentration and activity of lipopolysaccharides (endotoxin), phagocytic and bactericidal activity of neutrophils. The EAA (endotoxin activity assay) assessment should be conducted in conjunction with the neutrophil "response" assessment.

[The long-term infective complications in patients after kidney transplantation and photopheresis].

AIM: to evaluate the influence of prophylactic use of photopheresis on the risk of long-term infective complications after kidney transplantation. MATERIALS AND METHODS: The open cohort randomized study was conducted. A total of 60 recipients after cadaveric kidney allotransplantation from 30 donors were assessed. The patients were randomized into two groups (n=30). All transplants were paired, and one kidney was transplanted to patient in intervention group and the another one was transplanted to patient in control group. In the intervention group all patients received standard immunosuppression therapy (tacrolimus, mycophenolate, prednisone) and 10-15 sessions of photopheresis during first 6 months after the transplantation. In the control group only the immunosuppression therapy was given. The follow-up period ranged from 2 to 7 years, an average 4.5+/-2.0 years. RESULTS: The rate infective complications in the both groups gradually decreased as the postoperative period increased exponentially, but it was lower in the intervention group than in the control group. The rate of respiratory infection, asymptomatic bacteriuria and viremia, verified by the genetic amplification was 4, 2 and 1.5 times lower in the intervention group. The risk of clinically meaningful infection was significantly lower in the intervention group than in the control group: IRR 0.3888 (95% CI 0.2754; 0.5445; <0.0001). 6-year survival in the intervention group was 100% in comparison to 82.8% in the control group (95% CI 51.6; 93.16). CONCLUSION: The prophylactic use of the photopheresis allows to decrease the risk of infective complications after the kidney transplantation.

The impact of therapeutic plasma exchange and double filtration plasmapheresis on hemostasis in renal transplant recipients.

AIM: To investigate the impact of double filtration plasmapheresis (DFPP) and therapeutic plasma exchange (TPE) on hemostasis in renal transplant recipients. MATERIALS AND METHODS: 54 renal transplant patients with an acute humoral rejection were treated with therapeutic apheresis methods: 24 patients with DFPP and 30 patients with TPE. In all patients was performed 3-4 session. We analyzed international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration and platelet count just before and after each session, and after the course of all procedures. After TPE plasma replacement was performed with an equivalent volume of a fresh frozen plasma. After DFPP was performed 10-20% albumin solution. RESULTS: After each DFPP session was occurred an increased INR and aPTT. After course of all DFPP procedures fibrinogen level decreased by 46%. It was associated with increase of APTT and INR by 35% and 32% respectively. Mainly it was associated with dose of the procedures (volume of plasma perfusion), but not with the plasma separator type. One patient noted hemorrhagic complication. After each TPE session level of fibrinogen concentration, INR and aPPT remained in the normal range, but there was a moderate reduction in platelet count, more pronounced than during DFPP. Hemorrhagic complications were not. CONCLUSION: Double cascade plasmapheresis and therapeutic plasma exchange generate preconditions for hemorrhagic complications such as increased aPTT and INR, reduce fibrinogen concentration. However, bleeding complications are rare. At the same time, during high volume DFPP should be careful when initially level of fibrinogen is low. In this case fibrinogen concentration should be controlled after the procedure for timely replenishment of its deficit.

[The development of technique of evaluation of genes' expression level responsible for activation and inhibition of T-cell response in recipients of renal transplant under application of extra-corporal photochemotherapy.]

The article presents the developed and approved test-systems for evaluation of the level of expression of immune system responsible activation and inhibition of T-cell response in recipients of renal transplant under application of extra-corporal photochemotherapy.

[Renal transplantation in recipients with moderate presensitization]. / Transplantatsiya pochki u retsipientov s umerennym urovnem predsensibilizatsii.

AIM: to comparatively assess desensitization schemes with and without plasmapheresis in patients with low presensitization. SUBJECTS AND METHODS: The investigators studied the efficiency of the two desensitization schemes (cascade plasma filtration + intravenous immunoglobulin used in a dose of 100 mg/kg in 19 patients (a study group; panel reactive antibodies (PRA) 25.1±6.1%) versus 2 g/kg in 23 patients (a comparison group, PRA 18.9±4.4%). The crossmatch reaction was negative in both groups. The median follow-up period was 23.5 (quartiles 1 and 3: 10.25 and 26) months. RESULTS: The study group was noted to have 6 episodes of acute rejection and 1 episode of infection; the comparison group had 13 and 3 episodes, respectively. The overall renal graft survival was 79 and 65% in the study and comparison groups, respectively; the 1-year graft survival was 94 and 62%. Graft function was significantly better in the study group: there was a lower daily proteinuria level (p<0.001) at 3 months after transplantation; a higher glomerular filtration rate (GFR) (p=0.001) and a lower daily proteinuria level (p=0.01) at 6 months; a lower serum creatinine comcentration (p=0.001) and lower daily proteinuria (p=0.001) and a higher GFR (p=0.001) at one year. CONCLUSION: Even with the relatively low level of sensitization, there is an increase in the frequency of acute rejection episodes and worse graft function. The efficiency of desensitization using cascade plasma filtration and low-dose intravenous immunoglobulin is higher than that with high-dose intravenous immunoglobulin.

[Five-year analysis of microbial landscape of transplantation and dialysis center (20112015)].

INTRODUCTION: Treatment of bacterial infections is pressing and difficult task of modern transplantology. AIM: To analyze the spectrum of bacterial microflora and bacterial sensitivity to antibiotics in patients of the transplantation and dialysis center. RESULTS: The study analyzed the results of bacteriological tests performed in 534 patients with chronic kidney disease stage 5 in 2011-2015. Biomaterials for the examination included urine, blood, wound discharge and sputum. Gram-positive bacteria, Gram-negative bacteria, fungi and mixed flora were found in 42%, 39%, 4% and 15%, respectively. Among observed associations 51% were presented by a combination of Gram-positive and Gram-negative bacteria and the others were different combinations of fungi. The most often detected bacteria were Enterococcus spp. (37%), Klebsiella pneumoniae (25%), Staphylococcus spp. (19%), E. coli (13%), Streptococcus spp. (6%), P. aeruginosa (5%). Fungi of the genus Candida were isolated from 11% of all cultures. Enterococci and Klebsiella had pronounced resistance to most antibiotics. All gram-positive bacteria were highly sensitive to vancomycin and linezolid. DISCUSSION: The findings suggest that the percentage of Gram-negative bacteria that are resistant to antibiotics is increasing. CONCLUSION: Significant changes in the microbial landscape and the growing antibiotic resistance dictate the need for periodic analysis of the bacterial flora in the transplantation and dialysis center.

[Extracorporeal photochemotherapy as prevention of graft rejection, coupled with declining infectious complications rates in urological patients].

This study presents results of extracorporeal photochemotherapy (EPCT) application in 24 renal allograft recipients (RAR), who suffered chronic kidney disease (CKD) caused by urological diseases. The comparison group treated only with chemical immunosuppression comprised 24 recipients who received transplants from the same donors as intervention group patients. It was found that EPCT reduces not only the number of RAR rejections, but also the incidence of infectious complications. The effectiveness of EFHT was confirmed by clinical, laboratory and immunological data, and by protocol biopsy results. Possible mechanisms of preservation of anti-infectious protection in the setting of chemical immunosuppression when using EPCT are discussed.

[Impact of plasmapheresis on intraorgan blood flow of the transplanted kidney in the early postoperative period].

Kidney transplant is inevitably subjected to ischemic and reperfusion injury. In many cases, this is due to a violation of intraorgan hemodynamics. Severity of such damage can be reduced using different methods of extracorporeal hemocorrection. The aim of the study was to examine the intraorgan blood flow of kidney transplant and assess the impact of plasmapheresis on its primary function in the early postoperative period. Plasmapheresis with replacement from 1,25 to 3,5 liters of plasma was applied in 40 recipients of the Group 1; in 40 recipients of Group 2 plasmapheresis was not performed. High resistance index (Ri > 0,9) at low flow velocities in the interlobular arteries at the first day after surgery is an informative criterion for the diagnosis of acute tubular necrosis and indicates the inadequate blood supply of kidney. Plasmapheresis has promoted the normalization of renal hemodynamics. Immediate graft function in patients of Group 1 was observed in 36 patients, whereas only in 19 patients of Group 2. In the Group 1, there were no patients with primary non-functioning graft, while there were three such patients in Group 2. Thus, plasmapheresis in the early postoperative period, no later than 3-5 h after reperfusion of the graft, has a positive effect on the functional status of the transplanted kidney.

[Infectious complications after kidney transplantation].

The review of literature presents the current view of domestic and foreign authors on the frequency of infectious complications after kidney transplantation, their etiology, timing of emergence, and the spectrum of bacterial pathogens. Data on the effects of bacterial complications on the function of renal transplant and recipient survival are also demonstrated.

[Modern methods for extracorporeal detoxication in sepsis].

This review highlights current concepts of sepsis pathogenesis and the efficacy of modern methods of extracorporeal hemocorrection.

[Cellular factors of ischemia/reperfusion injury pathogenesis in the renal transplantation].

A review of literature reveales the current conception of Russian and foreign authors on the cellular and humoral pathogenetic mechanisms of ischemic and reperfusion injury of kidney transplant.

[The clinical course and treatment of fungal infections in the early period after kidney transplantation].

The article discusses the critical issues of clinical manifestations and treatment of fungal infections in patients after kidney transplantation. In fungal infection, which is usually detected in the composition of microbial associations, lungs are more often affected. In this case, mortality reaches 60%. Affecting the renal transplant by Candida spp. or Aspergillus spp. can lead to the loss of function of transplanted kidneys. At the current stage, lipid formulations of amphotericin B are drugs of choice for antimycotic therapy in posttransplant period. Nephrotoxic effect of amphotericin B is reversible and does not represent a serious threat to the function of the transplantate. Administration of lipid formulations of amphotericin B is the most justified, since it does not affect the concentration ofimmunosuppressive drugs in the blood serum of patients after transplantation.

[Kidney transplantation in recipients with renal carcinoma].

Transplantation of the kidney in patients with renal carcinoma is disputable. The article presents the results of kidney transplantation in different cancer lesions of the patient's kidneys. Seven case histories of patients with primary renal tumors are retrospectively analysed. A clinical case of development of the tumor of own kidney in a patient after transplantation is reported. A time factor of kidney transplantation after tumor removal in a recipient is discussed.

[Laparoscopic operations in patients with chronic renal failure on peritoneal dialysis].

The aim of our study was analysis of efficacy of laparoscopic operations for treatment of complications arising in patients with terminal chronic renal failure (TCRF) on peritoneal dialysis (PH). A total of 86 TCRF patients participated in the trial. The study group consisted of 36 patients who have undergone laparoscopic surgery for correction of dysfunction of the peritoneal catheter, for treatment of acute and progressive chronic diseases of the abdomen. A control group included 50 patients treated with laparotomy. All the patients were on the dialysis for 1-48 months. After laparoscopic operations 7 patients were switched on hemodialysis. In the control group peritoneal dialysis was discontinued in 30% patients, lethality in this group was twice higher. Thus, laparoscopic operations allow prolongation of peritoneal dialysis in dysfunction of peritoneal catheter and in development of acute and progression of chronic surgical diseases of the abdomen.

[Computer morphometry of lymphocytes in the diagnosis of chronic transplant nephropathy].

AIM: to assess the role of immunological mechanisms in the development and progression of chronic transplant nephropathy (CTN) and the prognostic value of rapid computer morphometry of lymphocytes in predicting the risk of renal allograft rejection. SUBJECTS AND METHODS: Thirty-seven renal graft recipients (29 males and 8 females; mean age 35.9 +/- 2.2 years; mean time after renal allografting 19.9 +/- 2.7 months). Twenty-three patients had satisfactory renal graft function; 14 patients were diagnosed as having CTN. A control group included 30 apparently healthy individuals. Along with physical examination, vital computer phase morphometry (CPM) of peripheral blood immunocompetent cells was carried out in all the patients. RESULTS: Small and average cells were predominant in the T and B lymphocyte populations. In CTN, there were increases in diameter, perimeter, and area and decreases in the phase height and volume of B lymphocytes, which is indicative of their activation. There was a predominance of average B lymphocytes in CTN. CONCLUSION: Vital CPM of peripheral blood immunocompetent cells may be used for the early diagnosis and prediction of CTN development.

[Characteristics of a 24-hour rhythm of blood pressure in patients with chronic renal failure on peritoneal dialysis].

AIM: To analyse 24-h rhythm of blood pressure (BP) and its influence on the rate and severity of left ventricular hypertrophy (LVH) in patients with chronic renal failure (CRF) on replacement therapy (peritoneal dialysis - PD). MATERIAL AND METHODS; 70 CRF patients on PD were studied. Their examination included clinical, biochemical tests, automatic 24-hour blood pressure monitoring, transthoracic echocardiography. RESULTS: Non-dipper and night-peaker disorders of BP 24-hour pattern were registered in 81.4% patients irrespective on hypertension severity. Left ventricular myocardial hypertrophy was 87.7% in patients with disturbed 24-h BP rhythm and 53.8% (p = 0.015) in normal BP rhythm. LV myocardial mass index median was 223 and 129 g/cm2 (p = 0.026), respectively. Concentric and excentric models of LV hypertrophy occurred with the same rate in normal and disturbed 24-h rhythm of BP. CONCLUSION: CRF patients on PD are characterized by disorders of 24-h BP rhythm independent of hypertension severity. Night-peaker pattern of BP is a risk factor of development and/or progression of LV hypertrophy.

[Some aspects of clinical kidney transplantation from marginal cadaver donors].

The results of kidney transplantation from marginal donors were compared in two groups of patients who had received high-dose dopamine (10-35 mcg/kg/min). Group 1 consisted of 652 patients with grafts from stable donors given dopamine in doses from 0 to 10 mcg/kg/min, group 2--of 112 patients with grafts from donors given high-dose dopamine (10-35 mcg/kg/min). Mean follow-up was 52 +/- 19 months. The following parameters were compared: percent of delayed graft function, primary nonfunction transplants, acute graft rejection, graft survival, biopsy-proven ischemic-reperfusion graft injury. The rate of delayed graft function, primary non function transplants was higher in group 2 (59 and 51%, 7 and 4%, respectively). Five-year survival of the transplants and recipients was less in group 2 (68 vs. 73% and 78 vs. 71%, respectively, p < 0.05). At the end of the follow-up the level of serum creatinine was 151 +/- 50 in group 1 and 165 +/- 80 mcmol/l in group 2 (p > 0.05). Thus, despite worse results in group 2, kidney transplantation from such marginal donors can be used.