[Immunosuppressive therapy as a risk factor for new-onset diabetes after transplantation].

AIM: To analyze the modes of immunosuppressive therapy as a risk factor for new-onset diabetes after transplantation (NODAT) in kidney recipients. MATERIALS AND METHODS: The retrospective analysis included data from 1367 recipients (755 men and 612 women) who lived more than one year after NODAT and were observed at the Moscow City Nephrology Center from January 1989 to December 2018. NODAT was established for 178 (13%) patients based on criteria from the World Health Organization and the American Diabetes Association. The modes of immunosuppressive therapy using cyclosporin A (CSA), tacrolimus (Tac), mTOR inhibitors, glucocorticoids in patients with NODAT and without NODAT were evaluated. To assess the impact of risk factors, descriptive statistics methods were used, the odds ratio (OR) and the 95% confidence interval (CI) were calculated. RESULTS: NODAT was diagnosed in 105 men and 73 women. The OR for men was 1.19 (95% CI 0.871.64), the OR for women was 0.84 (95% CI 0.611.15). At the time of transplantation, the average age of the kidney recipients in the NODAT group was higher than in the group without NODAT: 51 [43; 57] and 43 [32; 52] years, respectively (p=0.0001). Most patients with NODAT (82%) were older than 50 years, while in the group without NODAT, the proportion of patients of the same age was 48.5% (p=0.0001). Among patients without NODAT, transplantation of a kidney from a living donor was significantly more often compared with the group with NODAT+ (7.1% vs 1.1%;p=0.001). Among the recipients who received the regimen with CSA, diabetes developed in 75 (42.1%), those who received Tac in 102 (57.3%;p0.05). The chance (risk of development) of NODAT in patients receiving i-mTOR + Tac was 3.2 (95% CI 1.476.78;p=0.032), and for patients receiving i-mTOR + cyclosporin A, the chance of development NODAT was 1.95 (95% CI 0.884.35;p=0.044). CONCLUSION: 13% of recipients developed de novo kidney diabetes after allograft. Age at the time of allotransplantation, gender, as well as the use of tacrolimus in combination with i-mTOR are the most significant risk factors for the development of NODAT.

[Hyponatremia: A clinical approach]. / Giponatriemiia: klinicheskii podkhod.

Hyponatremia is the most common electrolyte metabolic abnormality in clinical practice. The unfavorable course of many diseases is associated with hyponatremia. Acute severe hyponatremia is life-threatening because cerebral edema may develop. Less obvious chronic hyponatremia increases the risk of balance problems, falls and fractures, especially in elderly patients. In any occasion, hyponatremia should not be now regarded only as a laboratory phenomenon in critically ill patients, but it necessitates a thorough clinical analysis of each individual case and appropriate therapy. The paper presents approaches to diagnosing and treating hyponatremia in various clinical situations.

[Complement System Abnormalities in Patients with Atypical Hemolytic Uremic Syndrome and Catastrophic Antiphospholipid Syndrome].

Background: The role of the alternative complement pathway (AP) abnormalities in the pathogenesis of aHUS is well studied. Clinical and morphological manifestations of atypical HUS and catastrophic APS are often similar. However, studies on the state of AP in patients with CAPS are virtually absent. Aims: The aim of our study was to assess the state of AP in patients with CAPS and aHUS. Patients and methods: The study enrolled 67 patients (pts) with a diagnosis of CAPS (28 pts) and aHUS (39 pts). Studies of the complement system are made of 10 pts with CAPS and 20 aHUS. Factor H, I, B, D content, functional activity of factor H, and complement components C3, C4 was determined in serum by ELISA kit. Results: Patients with CAPS and aHUS showed similar changes in complement biomarkers. The factor H level in the serum was significantly higher than the standard value. However, the specific activity of factor H reduced, mean rate 59% for aHUS and 26% for CAPS. The median value of factor D was twice higher than the normal range in both groups, indicating the activation of the AP. Conclusions: There are indications of an AP activation not only in pts with aHUS but in CAPS pts too. We suppose that the activity of factor H is a more sensitive indicator of complement system changes than factor H level. Patients with CAPS and aHUS have similar clinical and laboratory characteristics. However, CAPS is more severe, with the involvement of a larger number of vascular beds. Perhaps this is due to the double damaging effects on the endothelium ­ of antiphospholipid antibodies (aPL) and activated complement. So we hypothesize that CAPS can be called aPL-mediated TMA in pts with a complement system defect.

[Cardiac involvement in thrombotic microangiopathies].

AIM: To describe cardiac involvement in patients with acute thrombotic microangiopathy (TMA). MATERIALS AND METHODS: The case histories of 46 patients with proven TMA, including 17 patients diagnosed with atypical hemolytic uremic syndrome (aHUS) and 29 patients with catastrophic antiphospholipid syndrome (CAPS), were analyzed. RESULTS: Different documentarily verified signs of cardiac involvement were revealed in 6 (13%) patients (5 and 1 patients diagnosed as having aHUS and CAPS, respectively). Five patients developed myocardial involvement at disease onset in the presence of multiple organ dysfunction. CONCLUSION: Cases of cardiac involvement in TMA of various genesis are presented. The exact incidence of myocardial involvement and its prognostic value are unknown so far.

[NEWLY-DIAGNOSED CHRONIC KIDNEY DISEASE IN PATIENTS OF A THERAPEUTIC CLINIC: THE ROLE OF GFR CALCULATION BY THE CKD-EPI FORMULA].

AIM: to estimate the prevalence of newly-diagnosed chronic kidney disease (CKD) and its risk factors in patients of a therapeutic clinic, to evaluate the importance of GFR calculation using the CKD-EPI formula. Materials and methods: the study included 275 patients (275 (31.1%) men and 610 (68.9%) women) aged 18-89 (mean 59.5 13.95) years. GFR of 60ml/min/l.73 m3 or signs of kidney lesions were diagnosed as CKD. Possible risk factors of CKD were elucidated based on the results of a questionnaire that provided information on complaints, metabolic disorders, family histoty compliance with a healthy lifestyle. Arterial pressure and serum creatinine level were measured, BMI and GFR calculated in all patients. RESULTS: Medical histories of 58% of the 885 patients contained signs of CKD. Among the remaining 372 (42%) ones, 7.2% had proteinuria and 20.1% GFR of 60ml/min/1. 73/m3. The prevalence of newly diagnosed CKD was 27.3%. The use of the CKD-EPI formula allowed to diagnose CKD in 18% of the patients having the serum creatinine level within normal values. The overall prevalence of CKD in the study group was 14%. CONCLUSION: the prevalence of newly diagnosed CKD in patients of a therapeutic clinic was 2 7.3%. The use of the CKD-EPI formula facilitates diagnostics of CKD.

[Acute glomerulonephritis in the 21-st century].

The paper discusses the specific features of the current course of acute glomerulonephritis, the spectrum of its etiological factors, and clinical manifestations. The factors influencing the course and outcomes of acute glomerulonephritis, including the risk of its progression to chronic kidney disease, are specially depicted.

[Influence of physical rehabilitation on quality of life after renal transplantation].

BACKGROUND: Aim of this study was to evaluate the role of physical rehabilitation to improve the quality of life (QOL) of people after kidney transplantation. PATIENTS AND METHODS: Analyzes the results of treatment of 57 recipients (mean age 35 +/- 9.65 years) donor kidney at different times of the postoperative period. Depending on the physical rehabilitation program allocated 3 groups of patients: group II--physical rehabilitation was carried out only in the first week after surgery to prevent early postoperative complications, in group I--during the year; in group III combined 30 relatively healthy people do not need an organ transplant and with a mean age 33.7 +/- 8.7 years, leading a normal life, not engaged in regular recreational physical culture. Quality of life was assessed using a questionnaire SF36 at 1, 3, 6 and a 12 months after surgery. RESULTS: One year after surgery in both groups compared with preoperative indicators marked improvement according to all scales of the questionnaire. However, in group I indicators of quality of life were higher than in group II from 11.4 to 19.7%, and even some items questionnaire SF-36 is higher than in group III which is associated with the physical rehabilitation. CONCLUSION: It has been shown that exercises is an important component of treatment and rehabilitation after kidney transplantation and help improve both the psychological and the physical component of quality of life.

[Alterations of the complement system in patients with catastrophic antiphospholipid syndrome].

AIM: To investigate alterations of the complement system in patients with catastrophic antiphospholipid syndrome (CAPS). SUBJECTS AND METHODS: Four patients (2 men aged 23 and 40 years and 2 women aged 39 and 58 years) diagnosed as having CAPS, including 3 patients with systemic lupus erythematosus and secondary antiphospholipid syndrome (APS) and 1 patient with primary APS, were examined. The activity of the complement components C1-C5 and total hemolytic activity were determined in all the patients at the moment of an acute episode and in 1 patient after treatment. RESULTS: The activity of the studied complement components and total hemolytic complement activity proved to be significantly decreased in all the patients. That of complement components recovered after treatment using fresh frozen plasma. The possibility and mechanisms of complement system activation in the patients with CAPS are discussed. CONCLUSION: The preliminary results obtained by the examination of few cases may lead to the conclusion that the complement system may be involved in the development of CAPS.

[Morphological verification of renal lesion as a compulsory stage in the diagnosis of Fabry disease].

The paper describes a case of Fabry disease in a patient in whom kidney biopsy enabled the renal lesion be characterized in detail. Fabry nephropathy-associated kidney tissue changes, including renal lesion, have been verified using electron microscopy of renal tissue.

[Test strip evaluation of albuminuria for the early detection of chronic kidney disease in persons with different risks (the experience of the Health Centers of the Moscow Region)].

AIM: To evaluate albuminuria (AU) in the Moscow Region's dwellers visiting the health centers and to clarify its association with the proven and discussed risk factors (RF) of chronic kidney disease (CKD). SUBJECTS AND METHODS: A total of 1623 patients (390 (24%) men and 1233 (76%) women; mean age 46 +/- 16 years) were examined. Urinalysis using test strips was performed in all the examinees. AU was estimated by the following scale: normal AU (NAU) (< 10 mg/l), an initial increase (11-30 mg/l), a pronounced increase (31-300 mg/ml), very high AU (> 300 mg/ml). A questionnaire covering gender, age, patients' anthropometric data, comorbidities, healthy lifestyle adherence, and smoking was designed to assess possible RFs for CKD. Body mass index (BMI) was calculated. Medical history examination showed metabolic disturbances and cardiovascular diseases. RESULTS: The detection rate of NAU was 18%; the initial and pronounced increases were found in 40 and 41% of the examinees, respectively; the very high AU was in 1%. The first questionnaire items associated with AU > 30 mg/ml were complaints of edema, sternal pain, poor appetite, meat aversion, and constant thirst. The detection rate of AU > 30 mg/l in hypertensive persons was 51%. If the patients had diabetes mellitus or a history of increased blood glucose episodes, the detection rate of AU > 30 mg/l amounted to as much as 65.5%. Estimation of overweight and obesity indicated that AU of > 30 mg/l was found in 44 and 49% of cases, respectively (p < 0.001). Analgesic abusers, long-term smokers, and sedentary people were statistically significantly more frequently found to have AU of > 30 mg/l. CONCLUSION: The pronounced and very high AU was noted in more than 40% of those who had visited the health centers. A questionnaire survey makes it possible to reveal a variety of AU increase-associated factors that primarily reflect metabolic disturbances and cardiovascular diseases and to identify a risk group in order to study AU first. Particular emphasis should be placed on the examinees' lifestyle. Healthy lifestyle non-adherence is closely correlated with increased AU and may be regarded as a RF for CKD.

[Phosphate binders in chronic kidney disease: the positions of sevelamer].

The paper shows the role of phosphate binders in the correction of phosphorus and calcium metabolic disturbances in chronic kidney disease. The results of clinical trials demonstrating the efficacy and safety of sevelamer are discussed.

[Successful treatment of massive thrombosis of the vena cava inferior with nephrotic syndrome and chronic bilateral pulmonary artery thromboembolism in a patient with genetic thrombophilia].

A case is reported of a 23-year-old male patient who developed, after severe blunt injury of the lumbar region, massive thrombosis of the vena cava inferior (VCI), both renal veins, bilateral pulmonary artery thromboembolism (PATE), nephrotic syndrome (NS). In spite of anticoagulant therapy, the condition of the patient progressively aggravated for 1.5 year: thrombosis involved the ileac and femoral arteries on the right, thrombus floated in the right atrium with PATE recurrent episodes, pulmonary hypertension reached 120 mm Hg with formation of decompensated cor pulmnonale, proteinuria and hypoalbuminemia deteriorated, anasarca edema developed Multigenic thrombophilia was diagnosed (1 homozygous and 5 heterozygous mutations). A radical one-stage operation was successful: thromboectomy from the VCI, right ileac and left renal veins, thrombendarterectomy from the pulmonary arteries, suture of the interatrial septum defect, installation of cava-filter After the operation pulmonary pressure lowered to 40-45 mm Hg, right heart volume normalized, immunosuppressive therapy with prednisolone and cyclosporine led to nephropathy remission. The discussion covers mechanisms and factors (including genetic) of thrombosis progression, correlations between intravascular thrombosis, NS and chronic glomerulonephritis (possible NS development due to bilateral thrombosis of the renal veins and nephropathy role in thrombosis progression), approaches to conservative and surgical treatment of such patients. Global experience in conduction of pulmonary thrombendarterectomy and thrombectomy from VCI is reviewed (one-stage operations were not described earlier).

[Peculiarities of diagnostics of weakly symptomatic clinical course of chronic pyelonephritis].

The difficulty of early diagnostics of weakly symptomatic clinical course of chronic pyelonephritis (CP) is attributable to the lack of adequate methods. We used a novel Litos system diagnostic technology based on morphological analysis of dehydrated biological fluid The aim of the study was to develop methods for CP diagnostics from morphological characteristics of urine at different stages of the disease. It included 108 patients aged 58+/-1.3 yr with CP and 24 practically healthy subjects. Standard examination of all patients was supplemented by the analysis of urine using the Litos system. It was shown that morphological picture of urine makes it possible to objectively detect not only complete remission or exacerbation of the disease but also partial remission and high risk of CH even in patients with weakly symptomatic clinical course of this pathology. In case of incomplete remission, the treatment requires adequate long-term (three-course) antibacterial therapy despite normal results of urine analysis and microbiological studies. Patients at high risk of CP need to be prescribed preventive phytotherapy.

[Comparative characteristics of hemostasis system in patients with endstage renal disease admitted for urgent and elective hemodialysis].

AIM: To evaluate parameters of hemostasis system in patients with end-stage renal disease (ESRD) with consideration of elective or urgent start of dialysis treatment. MATERIAL AND METHODS: A total of 47 patients with ESRD entered the study. They were divided into two groups depending on urgent (group 1) or elective (group 2) start of hemodialysis. Group 1 consisted of 31 patients (13 female, 18 male) aged 18-86 years, group 2 - of 16 patients (9 female, 7 male) aged 36-79 years. The patients were comparable by ESRD causes. Clinical and laboratory findings were compared: activated partial thromboplastin time, prothrombin time, levels of fibrinogen, soluble complexes fibrin-monomers (SCFM). RESULTS: Azotemia, hyperkalemia and anemia were close to similar. Group 1 patients had more severe alterations of nutrition status and fat metabolism, marked hyperhydration and hypervolemia, arterial hypertension, more frequent neurological and infectious complications, symptoms of enteritis. Thrombotic complications developed in 51.5%, thromboses of the vascular access in 45% in group 1 vs group 2 which demonstrated only one type of thrombotic complications - thromboses of primary arteriovenous fistula (in 1 patient, 6.25%). Hemorrhagic complications were absent in group 2, in group 1 these developed 5 times less frequently than thromboses. Platelet count was significantly less (p = 0.001) in group 1 than in group 2. Hyperfibrinogenemia occurred in about 65% patients of group 1 and in 46% in group 2. SCFM levels were elevated in both groups, but in group 1 these levels were by 50% higher than in group 2 (p = 0.005). This evidences for stronger activation of intravascular coagulation in patients on urgent hemodialysis. CONCLUSION: ESRD patients admitted for urgent hemodialysis had more severe uremic syndrome with stronger activation of blood coagulation than patients admitted for elective hemodialysis. Frequency of thrombosis in patients admitted for urgent hemodialysis was 8.3 times higher than in patients admitted for elective hemodialysis.

[An experience of the use of angiotensin II receptor blocker losartan in patients with metabolic syndrome and chronic kidney disease].

Aim of the study--to assess efficacy and safety of one of angiotensin II receptor blockers in patients with metabolic syndrome (MS) and I-V stage chronic kidney disease. We studied cardiodynamic and renal effects of losartan in average daily dose 50 +/- 13.06 mg in 20 patients (9 men and 11 women aged 32-79 years) with MS and I-V stage chronic kidney disease. Cardiodynamic effects of losartan were assessed by office blood pressure (BP) measurements, 24-hour BP monitoring (24-HBPM), echocardiography. Laboratory investigations included biochemical analysis of the blood with measurement of creatinine levels, lipid blood composition, fasting glucose, and glucose under conditions of oral glucose tolerance test. Renal function was assessed by glomerular filtration rate and microalbuminuria (MAU). Parameters of quality of life were analyzed with the use of questionnaires "Quality of life of patients with hypertensive disease" and EuroQol EQ-5D VAS thermometer. Duration of follow up was 12 weeks. 24-HBPM revealed significant lowering of systolic and diastolic BP in all temporal intervals, significant decrease of elevated diurnal systolic and diastolic BP burden, tendency to lowering of variability and normalization of 24-hour BP profile. We also noted tendency to lowering of MAU from 5.60 mg/dl (median) (3.50; 9.20 [25th and 75th percentile]) to 3.25 mg/dl (0.40; 7.83); significant lowering of levels of triglycerides and glucose under conditions of glucose tolerance test; improvement of parameters characterizing quality of life namely reduction of integral assessment by the "Quality of life of patients with hypertensive disease" questionnaire and improvement of EQ-5D VAS (thermometer) score related to arterial hypertension. We conclude that losartan in patients with MS and early signs of impairment of kidney function in addition to antihypertensive action exerts favorable effect on parameters of 24-hour BP profile, has good safety profile, causes favorable metabolic effects, lowers level of MAU and improves parameters of quality of life.

[Autonomic imbalance in patients with metabolic syndrome: role in the development of hyperfiltration--an early marker of renal lesions].

AIM: to study the impact of the autonomic nervous system on the development of renal lesion in patients with metabolic syndrome (MS). SUBJECTS AND METHODS: One hundred and nine patients (45 females and 54 males) aged 29 to 72 years who had MS were examined. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault formula, by correcting the obtained result on the body surface. According to the level of GFR, the patients were divided into 3 groups: 1) 30 MS patients with hyperfiltration (GFR > 110 ml/min/1.73 m2); 2) 55 patients with normal GFR (110-60 ml/min/1.73 m2); 3) 24patients with lower GFR ( < 60 ml/min/1.73 m2). All the patients underwent physical examination; autonomic tonus was examined by 24-hour cardiac rhythm variability (CRV) study using the Holter monitoring system, by applying the time analysis. The presence of autonomic dystonia syndrome (ADS) and its degree were determined by a questionnaire to detect autonomic nervous system (ANS) dysfunction. RESULTS: Each of 3 groups was found to have signs of autonomic imbalance with a preponderance of sympathetic activity with decreased parasympathetic activity, these impairments being more pronounced in Group 1. The obtained regulation reflects the entire decrease in autonomic actions on the cardiovascular system in patients with MS and suggests the maximum hyperactivation of the sympathetic ANS in early-stage renal lesion--hyperfiltration CONCLUSION: When the first signs of renal lesion (hyperfiltration) occur in patients with MS, there is significant hypersympaticotonia that promotes the progression of target organs, including the kidneys.

[Current methods for measuring the glomerular filtration rate in persons with normal weight and overweight].

A steady increase in glomerular filtration rate is considered to be one of the first stages of renal lesion in essential hypertension, metabolic syndrome, and type 2 diabetes mellitus. The paper discusses methods for detection of hyperfiltration and gives their comparative characterization and indications for their use.