Vol 45, No 7 (2017)


Vascular access in patients on chronic hemodialysis in the Moscow Region: current state and outlook

Vatazin A.V., Zulkarnaev A.B., Fominykh N.M., Kardanakhishvili Z.B., Strugaylo E.V.


Background: The prevalence of chronic kidney disease (CKD) is annually growing worldwide. Stable functioning arteriovenous fistula (AVF) is one of the main prerequisites of survival for patients on chronic hemodialysis (HD). As a rule, available clinical guidelines for creation and maintenance of HD vascular access do not give a clear answer to some important questions. We have summarized and analyzed our experience of the creation and maintenance of the vascular access. Aim: To analyze the results of the creation and maintenance of vascular access in a large population of patients on chronic HD (in the Moscow Region). Materials and methods: We analyzed the results of 3837 surgeries for creation and reconstruction of the vascular access in 1862  patients, performed from 2012 to 2016. Results: The CKD stage 5D incidence has increased from 239 to 391 over the last three years. Currently, 2204  patients are followed up and receiving treatment in 38 outpatient centers. Almost one half of all interventions, 43.5% (1668/3837), has been performed to create AVF. Only one third, i.e. 33% (1266/3837) of them was de novo operations, whereas 10.5% (403/3837) were done to create a new AVF in HD patients after thrombosis of the existing AVF. 15.4%  (590/3837) of the interventions were performed for AVF reconstruction, 4% (154/3837) for AVF closure after successful kidney transplantation, 3.2%  (121/3837) for creation of AVF with vascular graft, 3%  (115/3837) for thrombectomy from the graft, 14.6%  (559/3837) to implant a  permanent central venous catheter (CVC), and 13.6%  (520/3837) for placement of a  temporary CVC. 54.4%  (1012/1862) of the patients had their functional AVF, 2.2% (41/1862) had a vascular graft at the beginning of HD, and one year later, there were 73.8% (1152/1561) and 5.3% (83/1561) of such patients, respectively. The type of vascular access at the start of HD strongly depended on the cause of CKD. 60.4% (192/318) of patients with polycystic kidney disease and 65.1% (181/278) with systemic disease or cancer started HD with the CVC. Oneyear survival of patients who started HD with AVF, who started HD with CVC and switched to AVF, and those who initiated and continued HD with CVC only, was 87.5% (95% confidence interval [CI] 83.5– 90.6), 79.6% [95% CI 72.3–82.5], and 66.4% (95% CI 57–74.2), respectively. The 5-year survival in these groups was 61% (95% CI 51.8–71.9), 53.9% (95% CI 42.5–67), and 31.6%  (95%  CI 21.4–41.4), respectively. At one year, primary and secondary AVF patency amounted to 77.2%  (95%  CI 71.7–81.8) and 87% (95% CI 83.7–89.7), respectively, at 5 years 34.1% (95% CI 27.8–40.5) and 60.9% (95% CI 56.4– 65.1), respectively. Conclusion: A more detailed analysis is necessary to identify risk factors for complications of the vascular access and to optimize approaches to its creation and reconstruction. An effective way to achieve this goal is to establish a local registry of CKD patients. 

Almanac of Clinical Medicine. 2017;45(7):526-534
pages 526-534 views

AB0-incompatible living donor kidney transplantation: the long-term outcomes

Moysyuk Y.G., Sushkov A.I.


Background: AB0-incompatible kidney transplantation is one of the ways to effectively expand the pool of living donors. In Russia, this technology has been used for more than 10 years, but until now there have been no reports on its long-term results. Aim: To evaluate the short- and long-term outcomes of the living-related AB0-incompatible kidney transplantations. Materials and methods: We analyzed the results of 49 consecutive AB0-incompatible kidney transplantations, performed from 2011 to 2017. Preoperative management of recipients included administration of rituximab and intravenous immunoglobulin, plasmapheresis and/or selective immunoadsorption, and combination of tacrolimus, mycophenolates and steroids. The target of anti-A/B antibody levels were is 1:8. All patients received standard immunosuppression after transplantation. Results: At baseline, median anti-A/B titer was 1:16 (1:2 to 1:1024) for IgM and 1:4 (0 to 1:512) for IgG. Median rituximab dose was 286 mg/m2 (range, from 94 to 396). To achieve target antibody levels, up to 10 plasmapheresis and/or immunoadsorption sessions (median, 2) were required. There were no deaths during the follow-up. Five grafts were lost, one of them due to hyperacute rejection. The incidence of biopsy-proven rejection was 6%. One-, three and six-year graft survival was 94%, 90% and 80%, respectively. Conclusion: Kidney transplantation across the AB0-incompatibility barrier is a  safe, successful and reasonable option to reduce the organ shortage. 

Almanac of Clinical Medicine. 2017;45(7):535-546
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Assessment of the functional activity of platelets in chronic kidney disease stage 5D

Zelenin K.N., Esayan A.M., Rumyantsev A.S.


Rationale: Thromboembolic complications in patients on hemodialysis have a  significant impact on the duration and quality of life. Aim: To study the functional status of platelets in chronic kidney disease stage 5D (CKD-5D). Materials and methods: We examined 61 patients with CKD-5D. The duration of renal replacement therapy was 133 (74 to 177) months. The functional activity of platelets was evaluated in the adenosine diphosphate and adrenaline tests. Results: The functional activity of platelets in the adenosine diphosphate test was reduced in 35 (57.4%) of patients and unchanged in 26 (42.6%) patients. The functional activity of platelets in the adrenaline test was reduced in 38 (62.3%), normal in 8 (13.1%) and increased in 15 (24.6%) patients. Conclusion: In our study, only the adrenaline test was able to identify hyperactivity of platelets. We believe therefore, that the test with adrenaline is preferred for the study of the functional activity of platelets in CKD-5D. 

Almanac of Clinical Medicine. 2017;45(7):547-552
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Successful pregnancy in a patient on regular hemodialysis awaiting kidney transplantation

Prokopenko E.I., Nikol'skaya I.G., Rybakova O.B., Novikova S.V., Upriamova E.Y.


Currently, the prevalence of chronic kidney disease in the general population is in the range of 8.7 to 18.4%, being at least 3% in women of childbearing age. Therefore, improvement of pregnancy outcomes in patients with chronic kidney disease is an important medical and social problem. In the past, pregnancy in women receiving the program hemodialysis (HD) was considered impossible. The first successful pregnancy in HD was described in 1971. Recently, pregnancy outcomes in dialysis patients significantly improved with an increase in the live births to 73–79%. It was shown that intensification of the dialysis program plays an important role in the achievement of a  favorable pregnancy outcome, with an increase in the number of sessions to 6 weekly, and the total weekly duration of dialysis of up to 24 hours and more. We present a  clinical case of a  favorable course of pregnancy that was eventually detected in a  patient on program HD during her examination before the kidney transplantation. Her dialysis program was intensified, with no subsequent complications characteristic of pregnancy in chronic kidney disease, such as hypertension, preeclampsia, severe anemia, and serious fetal growth retardation syndrome. At week 38 of gestation, programmed vaginal delivery was performed; a healthy girl was born who did not need any intensive care. The successful outcome of this pregnancy was due to intensive dialysis treatment, a multidisciplinary approach to pregnancy management, and thorough obstetric monitoring.

Almanac of Clinical Medicine. 2017;45(7):599-604
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Successful treatment of periodic disease and secondary AA amyloidosis in a colchicine-resistant patient

Rameev V.V., Bogdanova M.V., Kozlovskaya L.V., Mukhin N.A.


The paper demonstrates current opportunities of effective management of periodic disease as an autoinflammatory disorder based on a clinical case of colchicine-resistant Mediterranean fever. We present modern approaches to the autoinflammation hypothesis and its molecular mechanisms in periodic disease. Based on literature and our own research results, we consider approaches to evaluate autoinflammation activity and to monitor treatment efficacy. Clinical value of S100A12, a novel marker of the activity of neutrophilic autoinflammation, is demonstrated. 

Almanac of Clinical Medicine. 2017;45(7):605-615
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Evolution in the understanding of idiopathic membranous nephropathy pathogenesis: from experimental models to the clinic

Bobkova I.N., Каkhsurueva P.A., Stavrovskaya E.V., Filatova E.E.


Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. This review describes a 60-year history of MN study and represents an evolution in the understanding of its pathogenesis from experimental models to the clinic. Due to the development in 1959 of an MN animal model (active and passive Heymann's nephritis) the renal autoantigen podocyte-related protein megalin was identified. Experimental studies confirmed that the immune deposits consisting of megalin with circulating antimegalin antibodies are formed in situ. That leads to the complement activation providing with the membrane attack complex formation in the subepithelial space which causes a  sub-lethal podocyte injury with a  reorganization of their actin cytoskeleton and a  dissociation of slit diaphragm proteins. As the result, the permeability of the filtration barrier increases leading to the proteinuria. Thus, the understanding of an idiopathic MN pathogenesis evolved from an immune complex-mediated damage into a podocytopathy so the pathway for the other podocyte-related antigens search was opened. Mechanisms of podocytes damage were considered to be the leading ones in the human idiopathic MN development. Nevertheless, the searching for antigenic targets different from the megalin was continued for many years, as human podocytes do not express this protein. In the first decade of the 21st century such autoantigens as neutral endopeptidase, M-type phospholipase A2 receptor, and thrombospondin type-1 domain-containing 7A were identified. Furthermore, the leading role of autoantibodies directed against these podocyte targets was confirmed. New knowledge formed the basis for modern diagnostics and treatment methods of MN. 

Almanac of Clinical Medicine. 2017;45(7):553-564
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Anemia of chronic kidney disease: novel physiological approaches to therapy based on simulation of hypoxic response

Aitbaev K.A., Murkamilov I.T., Fomin V.V.


Anemia is a modifiable risk factor for the progression of chronic kidney disease (CKD) and is characterized by a  decrease in the hemoglobin level, the hematocrit, and the number of circulating red blood cells. In the pre-erythropoietin era blood transfusion was a  common practice for the adequate correction of anemia in patients with CKD. However, a  recombinant human erythropoietin, that was developed and implemented into a clinical practice three decades ago, made a revolution in the renal anemia treatment. Today the management of anemia is based on the use of exogenous erythropoiesis-stimulating agents, such as erythropoietin and its analogues, as well as an oral or parenteral administration of iron. Nevertheless, despite of the high efficacy in the majority of patients this approach has a  negative side. The hemoglobin excursions, increased risk of cardiovascular complications, as well as the development of iron deficiency and chronic inflammation become additional factors in the pathogenesis of anemia associated with the renal failure. In this regard, the development of effective and safe methods of anemia management in CKD is of immediate interest. New medications based mainly on physiological approach are developed. A pharmacological activation of hypoxia-inducible factor (HIF) response is one of them. HIF is the main hormonal regulator of erythropoiesis that stimulates the production of endogenous erythropoietin. It is known that in patients with renal failure, the activation of this factor in response to hypoxia is compromised, resulting in a lack of erythropoietin production. This review covers the new mechanistic views on the hypoxic regulation of erythropoiesis and the production of erythropoietin by the kidneys, and presents the newly discovered interactions between the synthesis of erythropoietin, iron metabolism, and the chronic inflammation. Besides that, ongoing clinical trials of pharmacological HIF activators, such as FG-4592, GSK1278863, AKB-6548, BAY85-3934 are also discussed as a  new comprehensive and physiological approach for the treatment of anemia associated with CKD. Preliminary results of the clinical trials demonstrated a high efficiency of HIF activators in the treatment of renal anemia including a high tolerability, an increase in hemoglobin level and its maintenance in the target range, an increase in general capacity for iron binding and a reduction in the serum levels of both ferritin and hepcidin. However, there are some safety-related problems that include proangiogenic and adverse cardiovascular and metabolic complications, so the possibility of their development should be thoroughly studied in long-term clinical trials. 

Almanac of Clinical Medicine. 2017;45(7):565-574
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Prevalence of cardiovascular disorders before and after renal transplantation

Martirosyan S.M., Kosmacheva E.D.


Renal transplantation is the optimal approach to management of patients with terminal end-stage renal failure (ESRF). The leading position in the mortality structure of recipients of kidney transplants belongs to cardiovascular disorders. The review analysis the causes and the role of arterial hypertension, myocardial hypertrophy, congestive heart failure, coronary artery disease, and dyslipidemia at different stages of chronic kidney disease (the initial pre-dialysis stage, the hemodialysis or peritoneal dialysis stage, and the post-transplant stage), as well as the possibilities of management of cardiovascular complications. Despite the fact that a  successful transplantation would lead to restoration of the renal function, the prevalence of post-transplant arterial hypertension remains significant and continues to be a major prognostic factor. Arterial hypertension in ESRF patients triggers myocardial and chamber remodeling, mediated by left ventricular hypertrophy. Left ventricular hypertrophy progression due to fibrotic proliferation underlies the systolic and diastolic dysfunction, as well as electrical instability of the myocardium, which leads to such clinical conditions as heart arrhythmias and congestive heart failure. The development of congestive heart failure in transplant recipients has been recognized as an unfavorable prognostic factor. The high prevalence of coronary artery disease among the kidney recipients is related to such risk factors as left ventricular hypertrophy, decreased myocardial contractility, anemia, hypertension, and diabetes mellitus. Screening for coronary artery disease in patients with ESRF awaiting for transplantation, with subsequent preventive revascularization, may reduce perioperative risks of adverse cardiovascular events and improve long-term results of transplantation. Disorders of lipid metabolism related to ESRF are an independent risk factor for coronary atherosclerosis and coronary artery disease. Even after a successful renal transplantation, dyslipidemia remains a  significant problem with its specific characteristics. In addition to its effect on cardiovascular morbidity, the lipid disorders can deteriorate renal function. Identification of potentially reversible risk factors for cardiovascular events and their early management are a  key strategy that determines the life longevity and quality of life in renal transplant recipients. A thorough screening for risk factors in this patient category is necessary to optimize their management.

Almanac of Clinical Medicine. 2017;45(7):575-585
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Acute drug-induced tubulointerstitial nephritis

Dyadyk A.I., Kugler T.E.


Currently, medications have the leading position in the development of acute tubulointerstitial nephritis. Antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs are the most common etiologic agents of acute tubulointerstitial nephritis. Various drugs produce ambiguous types of immune response. For instance, antibiotics may induce a systemic allergic reaction, including fever, skin rash, eosinophilia and arthralgia, whereas non-steroidal anti-inflammatory drugs and proton pump inhibitors may evoke a subclinical cell-modified response. Blood and urine tests, as well as renal ultrasound examination do not allow establishing a highly reliable diagnosis of acute tubulointerstitial nephritis. Therefore, renal biopsy is essential for the diagnosis. Morphological abnormalities include interstitial inflammation and tubulitis. In a patient who is on any medication and is having high serum creatinine levels, decreased glomerular filtration rate, and urine test abnormalities, the possibility of acute tubulointerstitial nephritis should be considered by the clinician; the disease can manifest at various time intervals after intake of the drug (from several days to months). Treatment approach is based first of all on immediate withdrawal of the nephrotoxic agent and possible administration of immunosuppressive therapy. Timely diagnosis and early administration of glucocorticoids in morphologically confirmed tubulointerstitial nephritis are critical for restoration of the kidney functioning. Chronic kidney disease can develop in some patients. Clinicians in any specialty have to know about potential negative consequences of the use of antibiotics, non-steroidal anti-inflammatory drugs, proton pump inhibitors and other medications and to consider nephrotoxic factors. 

Almanac of Clinical Medicine. 2017;45(7):586-598
pages 586-598 views

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