Signs Of Nephropathy Research Articles

COPEPTIN LEVEL IN PATIENTS WITH DIABETIC NEPHROPATHY WITH ACE GENE POLYMORPHISM

Aim of the study was to determine the copeptin level in the blood serum of patients with type 2 diabetes mellitus (T2DM) depending on the kidney’s function and accounting for the Alu Ins/Del (rs4646994) polymorphism of the angiotensin-converting enzyme (ACE) gene. Materials and methods: 146 patients with T2DM complicated by diabetic nephropathy (DN) were examined. Patients were divided into 4 groups according to the chronic kidney disease stage. Control group – 30 healthy subjects. Serum levels of copeptin and insulin were determined by ELISA using appropriate kits in accordance with the manufacturers' instructions. Genotyping was performed using TagMan allelic discrimination assay. Results. Our study has shown that the development of DN in T2DM is accompanied by a significant increase of copeptin level in blood serum compared with the control group and with diabetic patients without signs of nephropathy. The highest copeptin levels were found in patients with albuminuria and impaired glomerular filtration rate. In patients with T2DM, a significant linear correlation founded between copeptin level and serum creatinine (r = 0.247, p < 0.03). We found more significant violations of glucose metabolism in DN patients with high serum levels of copeptin compared with patients with normal values of this factor. In particular significant increase in serum, copeptin was accompanied by an increase in the HOMA index and insulin level. In patients with T2DM – carriers of the homozygous I/I genotype were founded a reliable association with increasing copeptin levelы in blood serum, in contrast to D/D and I/D genotypes. Conclusions. The highest copeptin levels were founded in carriers of the homozygous I/I genotype of the Alu Ins/Del polymorphism of the ACE gene. An increase in the copeptin level has a certain genetic determinism, and its high level correlates with impaired glucose metabolism and the development of nephropathy in T2DM. Serum copeptin can be considered as a diagnostic marker of renal and metabolic lesions in T2DM. Keywords: diabetic nephropathy, copeptin, arginine-vasopressin system, diabetes mellitus, angiotensin-converting enzyme, ACE gene polymorphism.

Vasopressin marker copeptin and the development of renal and metabolic disorders in patients with type 2 diabetes

Abstract. The aim of the study was to evaluate the possibility of using copeptin as a marker of renal and metabolic dysfunction in patients with type 2 diabetes.
 Methods: In this cross-sectional, observational study included 78 patients with type 2 diabetes mellitus complicated by diabetic nephropathy (DN) were examined. Patients were divided into 4 groups according to the stage of chronic kidney disease. Control group - 15 healthy subjects. Serum levels of copeptin and insulin were determined by enzyme-linked immunosorbent assay.
 Results: our studies have shown that the development of DN in type 2 diabetes is accompanied by a significant increase of copeptin concentration in blood plasma compared with controls and with diabetic patients without signs of nephropathy. The highest values of copeptin were found in the later stages of DN - in patients with albuminuria and impaired kidney filtration function. In patients with type 2 diabetes, a significant direct correlation was found between copeptin level and serum creatinine (r = 0.247, p <0.03). We found more significant violations of glucose metabolism in DN patients with high serum levels of copeptin compared with patients with normal values of this factor. In particular, an increase in serum copeptin was accompanied by a significant increase in the HOMA index and insulin concentration.
 Conclusions. Our data indicate that the copeptin level reflects the functional state of the kidneys and can be considered a diagnostic marker of renal and cardiovascular lesions in type 2 diabetes.

Association Between Serum Asprosin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus in the Community: A Cross-Sectional Study.

ObjectiveTo explore the association between serum asprosin and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) in the community.MethodsIn this cross-sectional study, we retrospectively collected the clinical data of T2DM patients from a community health service center in southeastern Shanxi Province between November 2019 and July 2021. Logistic regression analysis was used to calculate the odds ratio (OR) and the 95% confidence interval (95% CI) of asprosin levels on the risk of DN.ResultsAmong 498 T2DM patients included in this study, 221 had microalbuminuria, 105 had massive albuminuria, and 172 did not have any signs of nephropathy. Serum asprosin level was positively correlated with diastolic blood pressure, body mass index, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine, ACR and albumin-to-creatinine ratio (all P < 0.05) and negatively correlated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, HbA1c and estimated glomerular filtration rate (all P < 0.05). After adjusting for covariates, increased asprosin was associated with diabetic nephropathy (all OR = 2.560, 95% CI: 1.1592–4.116; P < 0.001).ConclusionThe risk of DN significantly increases with serum asprosin levels, especially among female patients.

MO110: Ultrasound Evaluation of Post-COVID Kidney Disease

Abstract BACKGROUND AND AIMS COVID can affect many organs including kidneys involving various possible pathophysiological mechanisms [1]. Post-COVID conditions require focused approach for diagnosis, personalized treatments and rehabilitation. Ultrasonography (US) can provide accurate information for detecting kidney disease [2]. Shear wave elastography (SWE) is a recognized ultrasound method, still having a limited use in nephrology, yet can be used for early detections of kidney abnormalities. The aim of this study was to evaluate semiotics and the added diagnostic value of US for post-COVID kidney disease. METHOD We included 20 cases to the study (23–68 years; 8 women) who underwent COVID-19 during last 3 months with signs of kidney disease (proteinuria, increased levels of creatinine, uric acid in blood, hypertension) and other clinical, laboratory symptoms of nephropathy after COVID-19 without specific data of previous history of kidney disease. The control group included 20 healthy individuals (9 women), with mean age 37 ± 7 years without clinical, laboratory signs of nephropathy according to disease history. All patients underwent general clinical, lab tests; abdominal US including precise multiparameter US of kidneys as in [2] measuring renal resistive index (RI), did SWE, and sensitive Doppler (B-flow and similar) in parenchyma and vessels using curved abdominal transducer of US systems: LOGIQ 9 (GE Healthcare), Toshiba Aplio and Hitachi Arietta. RESULTS We detected US changes in all age groups, both in females and males. Severe kidney disease signs included thinning, increasing echogenicity of kidney parenchyma (P &amp;lt; .05), detection of fibrotic changes and small hyperechoic inclusions, hilly margins, anaechoic strips under the capsule, RI increasing in segmental arteries over 0.75, and decreasing velocities under 25 cm/s. SWE showed increased parenchyma stiffness to 10 ± 1.7 kPa (6–13 kPa) versus 4.2 ± 1.2 kPa (P &amp;lt; .05). Moderate changes included mild decrease of kidney medullary differentiation, RI increasing in segmental arteries over 0.7; parenchyma stiffness increased to 7.2 ± 1.5 kPa (5–10 kPa), P &amp;lt; .05. In 16 patients we diagnosed hypertension; all patients had increased RI over 0.75; pyelonephritis was in 2 patients. Three patients had the following abnormalities: amyloid kidney after COVID-19 was in two patients (male 62 years and female 58 years) manifesting on US with increased echogenicity small kidney, decreased blood flow and increasing RI (Figure 1). One patient had collapsing glomerulopathy [3] manifesting with proteinuria; kidney biopsy with immunohistochemistry performed 1 month after beginning of COVID-19 showed collapsing focal segmental glomerulosclerosis; US symptoms were unspecific (Figure 2). CONCLUSION Multiparameter ultrasound is an effective method for early detection of various types of kidney disease in patients after coronavirus disease, potentially effective to distinguish signs of nephropathy associated to COVID-19. Evaluation of renal RI and increased stiffness of kidney parenchyma are reliable markers.

Parameters of cardiac hemodynamics in patients with diabetes mellitus with impairment of renal function

Currently, diabetes mellitus (DM) is a complex global problem, which is increasing every year. So, in 2019, diabetes mellitus was detected in 463 million adults (from 20 to 79 years old) in the world. And the main cause of death in patients with diabetes mellitus is cardiovascular complications. The study was aimed investigate the features of functional and structural changes in the heart in patients with type 2 diabetes mellitus and nephropathy. A total of 98 patients with type 2 diabetes mellitus were examined, out of which 78 patients had diabetic nephropathy (DN) of varying severity. The control group consisted of 20 healthy patients. After a clinical examination, depending on the state of renal function, all patients were divided into the following groups: group I — patients with type 2 diabetes mellitus without signs of nephropathy (n = 36), group II — patients with type 2 diabetes mellitus with normal glomerular filtration rate (GFR) and albuminuria (n = 33), group III — patients with type 2 diabetes mellitus with decreased GFR and albuminuria (n = 29). To study changes in hemodynamics and structural parameters of the heart, patients underwent transthoracic echocardiography on an ULTIMA PA ultrasound machine (Radmir, Ukraine) using a sectoral phased transducer with a frequency range of 2–3 MHz according to the standard technique based on the recommendations of the American Echocardiographic Society. To determine indexing indicators, the patients underwent anthropometric measurements. Patients with DN and albuminuria and decreased GFR showed an increase in the linear dimensions of the heart in comparison with controls and patients without signs of nephropathy. With DN, patients have a significant increase in left ventricular mass and a significant increase in the detection rate of left ventricular hypertrophy up to 91.3 % in patients with albuminuria and preserved renal function and up to 100 % with a decrease in GFR.

Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset

Aim This study aimed to determine the earliest markers of diabetic nephropathy (DN) onset with discriminative potentials from controlled diabetes (CD). Methods Sixty male Wistar rats were allocated into three groups (20/group), the two diabetic groups CD and DN received 45 and 65 mg/kg STZ in 0.1 mole/L citrate buffer, respectively, while the control group received only the vehicle. Serum/urinary levels of glomerular, tubular, oxidative and proinflammatory markers were weekly monitored. Results Each diabetic group showed a different pattern of inflammatory, oxidative and signs of nephropathy along the study period, but none had a discriminative power until the fourth week. At this time point, levels of urinary transferrin, serum/urinary IL-6 and TNF-α as well as urinary IL-18 were significantly higher in DN group compared to CD (p = 0.0217, <0.0001, 0.0005, 0.0004, 0.0006, 0.0019, respectively). Predictive thresholds of these markers were calculated by receiver operating characteristic (ROC) curve that showed area under curve (AUC) of 0.9375 for transferrin with cut-off value of 35.2 mg/dL and 1.000 for serum/urinary IL-6 and TNF-α and urinary IL-18 with cut-of values 224.1, 82.11, 6.596, 125.9 and 21.86 pg/mL, respectively. Conclusion Urinary transferrin and the inflammatory endpoints proposed in this study might represent promising biomarkers for the early DN onset.

A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients.

Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and β-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance.

Протизапальний ефект нефропротекторної терапії у хворих на діабетичну нефропатію

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of chronic kidney disease worldwide. The majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The progression of fibrotic processes in the diabetic kidneys occurs with the participation of universal mediators of inflammation. Given the clinical and social significance of diabetic kidney damage, the determination of interleukin-1β and interleukin-6 in blood serum may expand the understanding of this problem, as well as help in the development of individualized therapeutic approaches. The purpose of the study is to investigate interleukin-1β and interleukin-6 levels in the serum of patients with type 2 diabetes mellitus, depending on kidney functional state in the dynamics of therapy and with additional prescription of dapagliflozin. Materials and methods. 72 patients with type 2 diabetes were examined. The control group consisted of 20 healthy individuals. The patients were divided into the following groups: group I – type 2 diabetic patients with normal glomerular filtration rate and without albuminuria (n = 25); group II – patients with type 2 diabetes with normal glomerular filtration rate and albuminuria (n = 23); group III – patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria (n = 24). The complex pathogenetic therapy of patients of group 1 included renin-angiotensin-aldosterone system blockers, metformin and hypolipidemic agents. Patients of group 2 were additionally prescribed dapagliflozin. The control was carried out after 6 months. Results and discussion. According to the results of the study, the development of diabetic nephropathy in patients with type 2 diabetes is accompanied by a significant increase in the level of interleukin-1β and interleukin-6 in the blood plasma compared with the control and in patients with diabetes without signs of nephropathy. Nephroprotective therapy contributed to a significant decrease of interleukin-1β and interleukin-6 levels in the blood serum in all groups of patients. The highest response to treatment was observed in patients with diabetic nephropathy and albuminuria. Most significant decrease of albuminuria, normalization of blood pressure and lipid spectrum improvement were observed in patients with the initial stages of the disease. Additional using of dapagliflozin leads to a more significant decrease in the content of proinflammatory cytokines in the blood serum of patients with type 2 diabetes mellitus with diabetic nephropathy. Conclusion. The results of the study indicate the advisability of using interleukin-1β and interleukin-6 as a diagnostic marker of cardiac disorders, assessment of prognosis, and improvement of the cardionephroprotective strategy in diabetic patients. The therapeutic potential of dapagliflozin in the treatment of diabetic nephropathy and the prevention of cardiovascular events in patients with diabetes is of great scientific interest and requires further research

Indicators of hemodynamic and structural heart parameters in patients with comorbid pathology

Currently, diabetes mellitus is a complex global problem, which is increasing every year. So in 2019, diabetes in the world was detected in 463 million adults (from 20 to 79 years old). And the main cause of death in patients with diabetes mellitus is cardiovascular complications. The features of functional and structural changes in the heart were studied in patients with type 2 diabetes mellitus and nephropathy. A total of 75 patients with type 2 diabetes mellitus were examined, of which 50 patients had diabetic nephropathy of varying severity. The control group consisted of 20 healthy individuals. The control group consisted of 20 practically healthy patients. After a clinical examination, depending on the state of renal function, all patients were divided into the following groups: group I consisted of 25 patients with type 2 diabetes mellitus without signs of nephropathy; group II consisted of 26 patients with type 2 diabetes mellitus with normal glomerular filtration rate and albuminuria; group III consisted of 24 patients with type 2 diabetes mellitus with decreased glomerular filtration rate and albuminuria. To study changes in hemodynamics and structural parameters of the heart, patients underwent transthoracic echocardiography on an ULTIMA PA ultrasound machine (Radmir, Ukraine) using a sectoral phased transducer with a frequency range of 2–3 MHz according to the standard technique according to the recommendations of the American Echocardiographic Society. Indicators the patients underwent anthropometric measurements. Patients with diabetic nephropathy and albuminuria and decreased glomerular filtration rate showed an increase in the linear dimensions of the heart in comparison with controls and patients without signs of nephropathy. With diabetic nephropathy patients have a significant increase in left ventricular myocardial mass and a significant increase in the detection rate of left ventricular hypertrophy up to 91.3 % in patients with albuminuria and preserved renal function and up to 100.0 % with a decrease in glomerular filtration rate. Keywords: diabetes mellitus, hypertonic disease, diabetic nephropathy, heart remodeling, chronic kidney disease.

Features of development of diastolic heart dysfunction in patients with comorbid pathology depending on the functional state of the kidney

The development of complications of diabetes mellitus and hypertension, in particular kidney and heart damage, mutually reinforcing each other, not only affect the quality of life, but also significantly reduce its average duration. One of the common problems in patients with comorbid pathology is the high prevalence of chronic heart failure. Very often chronic heart failure develops with a preserved left ventricular ejection fraction. These changes are associated with the diastolic phase of the heartbeat - diastolic dysfunction. The features of the development of diastolic dysfunction in patients with type 2 diabetes in combination with hypertension depending on the functional state of the kidneys were studied. After the initial examination, depending on the functional state of the kidneys, all examined patients were divided into three groups: first group consists of 25 patients with type 2 diabetes without signs of nephropathy; second group consists of 23 patients with type 2 diabetes with normal glomerular filtration rate and albuminuria; third group consists of 20 patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria. The control group consisted of 20 healthy patients. To study the state of the heart, transthoracic echocardio­graphy was performed on a ULTIMA PA ultrasound machine (Radmir, Ukraine) with a sectoral phased transducer with a frequency range of 2-3 MHz, according to the standard technique according to the recommendations of the American Echocardiographie Society. The data obtained confirm the need for prevention, early diagnosis, clarification of mechanisms and adequate treatment of diastolic dysfunction in diabetic nephropathy patients even before the onset of renal failure. Structural changes in cardiomyocytes activate the processes of apoptosis, enhancing the production of extracellular matrix, and contribute to the formation of myocardial fibrosis. Fibrous changes lead to the progression of impaired contractile function and an increase in the stiffness of the left ventricle walls, which leads to diastolic and systolic dysfunction and the development of heart failure. Diastolic myocardial function in diabetic nephropathy is complicated with the progression of the disease. Keywords: diabetes mellitus, hypertonic disease, diabetic nephropathy diastolic dysfunction, chronic kidney disease.

P1814ATYPICAL FEATURES IN A TYPICAL DISEASE: ONE THOUSANDS FACES OF IGA NEPHROPATHY IN PAEDIATRIC PATIENTS

Abstract Background and Aims Immunoglobulin A Nephropathy (IgAN) is the most common cause of idiopathic glomerulonephritis in paediatric patients. The typical presentation is characterized by recurrent episodes of macroscopic haematuria or persistent microhaematuria with mild or overt proteinuria. Renal function is normally preserved, though a slow progression to chronic kidney disease (CKD) may occur. However, in rare cases IgAN may assume atypical features, presenting with nephrotic syndrome (NS), acute kidney injury (AKI) or assuming the characteristic of a rapidly progressive glomerulonephritis, leading to significant difficulties in management and critical impact on prognosis. Method Of total 756 renal biopsies performed in our centre from 2000 till 2019, 174 (23%) diagnosis of IgA nephropathy were made: 123 (70,6%) of 174 with a milder histological stage (I or II according to Lee’s) and 51 (29,3%) with severe stages (III-IV). Clinical onset of these 51 patients was mostly characterized by a nephritic syndrome with micro-macrohaematuria, though in 7 of them it assumed atypical features (table 1). Results Patients 1, 2, 3 and 4 showed a rapidly progressive IgAN with extensive crescentic lesions at histological evaluation. In all of the four patients the onset of the disease was characterised by a compromised renal function, thought, according to the medical history, in patients 2 and 4 clinical signs of nephropathy had started some months before the first medical evaluation. This detail, considering the poorer clinical outcome of patients 2 and 4 (table 1), strongly highlights the need of promptness in the treatment of these conditions. Patient 1 achieved a complete remission after steroid pulse therapy (Pozzi scheme), while for patients 2,3,4 an additional immunosuppressive treatment was required. The nephropathy of patient 5 was, instead, characterized by AKI with consistent macrohaematuria. Interestingly, the severity of the clinical presentation was not related to the glomerular lesion (the histology showed a minimal change disease), rather to the intra-tubular haemorrhage, causing an obstructive acute kidney injury. Patient 5 achieved a complete remission after steroid treatment. The onset of IgAN in patients 6 and 7 was characterized by a nephrotic syndrome, which is a very uncommon feature (&amp;lt;2% of all IgAN). Patient 6, who showed a massive proteinuria (till 11 grams/24 hours) was promptly treated with steroid and tacrolimus, achieving a complete remission in 6 moths. Patient 7, a sri-lankan girl, was diagnosed in 2008 in Sri-Lanka. She underwent treatment with steroid and Mycophenolate and successively, for the persistence of proteinuria, with Cyclosporine A. From 2014 she has been followed by our centre. Despite a second cycle with Cyclosporine she has shown a persistence of proteinuria and a slow progression to CKD. Conclusion This study highlights that a typical disease like IgAN may hide behind an atypical and severe presentation. Moreover, the blackboard of the atypical forms is extremely heterogeneous, stretching from NS to crescentic and progressive diseases. As a consequence, the treatment of these conditions is not codified and represents an important challenge for the clinician. This calls for multicentric studies which could provide shared recommendation for the management of these atypical forms of IgAN.

The level of vascular endothelial growth factor in peripheral blood of type 2 diabetic patients depending on kidney functional state

Abstract. The aim of the study was to assess a serum level of vascular endothelial growth factor (VEGF) in type 2 diabetic patients depending on kidney function.&#x0D; Methods: we examined 66 type 2 diabetic patients and 20 healthy control subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR) level, patients with diabetes mellitus (DM) were divided into the following groups: group I - patients with type 2 DM without signs of nephropathy – normal GFR without albuminuria (n = 26); group ІІ - patients with type 2 DM with normal GFR and albuminuria (n = 22); group III - patients with type 2 DM with reduced GFR and albuminuria (n = 18). ІV group - patients with acute coronary syndrome (n = 26).&#x0D; The concentration of the VEGF was determined by enzyme-linked immunosorbent assay. The glomerular filtration rate (GFR) was calculated using the CKD EPI formula (KDIGO 2012).&#x0D; Results: serum VEGF level in patients with diabetic nephropathy (DN) was significantly increased depending on kidney function.&#x0D; VEGF positively correlated with urine albumin and serum creatinine levels and the negative correlation with GFR was found. These findings prove the undeniable role of kidneys in the development of renocardial syndrome in patients with DN. VEGF levels positively correlated with glycosylated hemoglobin and total cholesterol, indicating an unconditional dependence of endothelial dysfunction on lipid and glucose metabolism disorders.&#x0D; Conclusions: Increased levels of VEGF in type 2 diabetic patients without clinical signs of kidney damage may indicate the development of subclinical renal dysfunction. Blood VEGF in patients with DN may be an integral marker of endothelial dysfunction and pathological angiogenesis. Our findings suggest that determination of serum VEGF level in patients with DN may have practical use as an early predictor of cardiac disruption, estimation of the prognosis, as well as improvement of cardionephroprotective strategy.

STILL’S DISEASE IN A DULTS (CLINICAL CASES)

Objective: to analyse and describe clinical cases of Still’s disease in adults and peculiarities of therapy in patient with a monocyclic course of the disease who had at the beginning of the observation a high systemic account (12) and in patient with a recurrent course of the disease with a positive result for 25 and 10 years of a dynamic observation. Materials and methods. Patient L., a female, 35 years old, was taken to the therapeutic department of the clinic with fever of 38–39 °С, chills and sweating, resistant not itching rash, lymphadenopathy, signs of myocarditis, loss of 20 kg of weight, exudative pleurisy, pronounced orthopnea with respiration rate of 40–48, tachycardia up to 130 beats per minute, myalgia, hepatosplenomegaly and abdominal pains. In past medical history for 2 months of the disease the patient was examined, and the sings of disease progression were present. The clinical constellation in patient L. allowed us to formulate a diagnosis of Still»s disease. Some investigations were conducted repeatedly to track the changes. The following therapy by Indomethacin in a daily dose of 150–200 mg/day for 1 year and for 6 months in combination with D-penicillamine in a dose of 450 mg/day induced remission. Till the end of 2016 the disease recurrence was not revealed. In another patient B., a male of 57 years old, the disease manifested with sub-febrile temperature, pain in a testicular area, thrombocytosis, and the symptoms increased in 2 weeks and included resistant febrile temperature, lymphadenopathy, changes of laboratory tests, signs of nephropathy and encephalitis. The patient was examined to exclude oncology. Results. Still’s disease was diagnosed and the following therapy was administrated: diclofenac and methotrexate for 4 years with episodes of disease recurrence in case of decreasing the doses of the medications, but in future the therapy managed to cancel, and there was no recurrence observed. Conclusion. These clinical cases have demonstrated peculiarities of course, diagnostic and management of patients with Still’s disease, the possibility of prescribing non-steroidal anti-inflammatory drugs and synthetic basic anti-inflammatory drugs for achievement of persistent disease remission.

ВЛИЯНИЕ СУБКЛИНИЧЕСКОЙ НЕФРОПАТИИ НА СУБЪЕКТИВНУЮ ОЦЕНКУ ЗДОРОВЬЯ ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ 2 ТИПА

Цель. Оценить влияние субклинической нефропатии на показатели качества жизни пациентов с СД 2 типа и сердечно-сосудистыми заболеваниями.Материалы и методы. Обследовано 86 больных с СД 2 типа и сердечно-сосудистыми заболеваниями. Обследование пациентов проводилось 2-х кратно с интервалом в 12 месяцев. Сформировано 2 группы пациентов: группа 1 – пациенты с впервые выявленными маркерами повреждения почек (n=28); группа 2 – без маркеров повреждения почек (n=58). Для оценки качества жизни использована русифицированная версия опросника EQ-5D.Статистическая обработка результатов проводилась с использованием компьютерной программы Statistica for Windows 6.0 (StatSoft Inc., США).Результаты. Сравниваемые группы на момент включения по параметрам КЖ не различались. У пациентов, отнесенных к группе 1, оценка в баллах качество жизни по аналоговой шкале была выше группы 2.Через 12 месяцев в группе 1 не выявлено динамики баллов по визуальной аналоговой шкале, выявлена отрицательная девиация составляющих качества жизни; в группе 2 статистически значимо улучшилась оценка в баллах по визуально-аналоговой шкале. В группе 1 выявлена большая доля лиц, у которых были снижены показатели, характеризующие физическую составляющую качества жизни. Напротив, в группе 2 улучшилось качество жизни и по физическим, и психоэмоциональным компонентам. Таким образом, у пациентов с признаками субклинической нефропатии выявилось ее негативное влияние на компоненты качества жизни.Заключение. Появление признаков дисфункции почек у больных с СД 2 типа и сердечно-сосудистыми заболеваниями ассоциируется со снижением качества жизни. Полученные данные подчеркивают важность профилактики развития дисфункции почек, коррекцию факторов риска и прогрессирования нефропатии.

A SUCCESSFUL TREATMENT OF IMMUNOTACTOID GLOMERULOPATHY IN A PATITNT WITH MULTIPLE MYELOMA

ITG (immunotactoid glomerulopathy) cases in patients with multiple myeloma (MM) are extremely rare. We present a clinical case of a patient with MM Gκ who developed nephrotic syndrome, macrohematuria and acute kidney injury. Kidney biopsy revealed microtubules in glomerular basement membrane 19 nm in diameter, organized in bundles. The patient was treated with bortezomib, cyclophosphamide and dexamethasone (BorCyDex) and achived complete remission after 6 cycles of therapy with a complete renal function recovery. Repeated renal biopsy has revealed a complete resorption of the deposits. Later the patient has received autologous hematopoietic stem cells transplantation (auto-HSCT). After 2 years, an immunochemical relapse of MM has developed. Nephropathy signs have appeared 4 years after auto-HSCT, ITG was diagnosed again on kidney biopsy during MM relapse with microtubules 11-12 nm in diameter. A special characteristic of our case was excessive glomerular infiltration by the lymphoid cells with capillary lumen obstruction. We consider the build-up of lymphoid cells in the glomerulal capillaries lumen as a special variant of renal tumor lesion in MM. Lymphoid cells had signs of plasmatization. Bundles of microtubules, similar to the deposits in kidneys, were revealed in some of lymphoid cells. The data obtained confirm that microtubules are formed in plasma cells that situated in the lumen of glomerular capillary vessels and later migrate into renal structures.

Relationship of morphological changes of blood cells with endothelial function, renal function and lipidemic profile in patients with type 2 diabetes mellitus with suboptimal glycemic control and hypertension.

Background. Many questions about the relationship between endothelial dysfunction and morphological substrate of hemostasis damage that occur during the progress of type 2 diabetes mellitus and arterial hypertension require clarification and further advance. Objective. The aim of this study is to determine the relationships between endothelial dysfunction, the degree of renal function damage, lipidemic profile and morphological changes of vascular-platelet hemostasis in patients with type 2 diabetes mellitus with suboptimal glycemic control and hypertension. Methods. In 87 patients with insufficient glycemic compensation using clinical, laboratory, morphological methods and correlational analysis were identified association between endothelial dysfunction, degree of renal function damage, lipidemic profile and morphological changes of vascular-platelet hemostasis. Results. Against the background of insufficient glycemic compensation glycated hemoglobin concentration tightly correlated with the share of activated platelets (r=+0.77; p<0.05), with the level of aggregated forms (r=+0.82; p<0.05) and the concentration of small blood platelet aggregates (r=+0.76; p<0.05), established a positive relationship with the share degranulated platelets (r=+0.60; p<0.05). Signs of atherogenic dyslipidemia triad that this contingent of patients indicated significant deviation from that of the control group not only had a correlation with the share of activated platelets and content of alpha and delta granules, but also formed a new moderate strength correlations with other observable parameters of platelet morphology. In particular, amid insufficient glycemic compensation formed reliable values of the coefficients of linear correlation in pairs: total cholesterol and activated platelets (r=-0.54), low density lipoprotein cholesterol and activated platelets (r=-0.51), low density lipoprotein cholesterol and aggregated forms (r=+0.59), low density lipoprotein cholesterol and degranulated platelets (r=+0.48). Also triglycerides level in these patients established statistically significant correlation with all studied parameters of intravascular platelet activation. Conclusion. It has been established that in the insufficient glycemic control by a significant strengthening relationships between indicators of endothelial dysfunction and damaged platelet hemostasis formed significant correlations of ultrastructural characteristics of platelets with clinical and laboratory signs of nephropathy and dyslipidemic changes.

Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk.

Neuregulin-1 (NRG-1) is an endothelium-derived growth factor with cardioprotective and antiatherosclerotic properties and is currently being tested in clinical trials as a treatment for systolic heart failure. In clinical practice, heart failure often coexists with renal failure, sharing an overlapping pathophysiological background. In this study, we hypothesized that NRG-1 might protect against cardiomyopathy, atherosclerosis, and nephropathy within one disease process. We tested this hypothesis in a hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) type 1 diabetes mouse model prone to the development of cardiomyopathy, atherosclerosis, and nephropathy and compared the effects of NRG-1 with insulin. Upon onset of hyperglycemia induced by streptozotocin, apoE(-/-)mice were treated with vehicle, insulin, or recombinant human (rh)NRG-1 for 14 wk and were compared with nondiabetic apoE(-/-)littermates. Vehicle-treated diabetic apoE(-/-)mice developed left ventricular (LV) dilatation and dysfunction, dense atherosclerotic plaques, and signs of nephropathy. Nephropathy was characterized by abnormalities including hyperfiltration, albuminuria, increased urinary neutrophil gelatinase-associated lipocalin (NGAL), upregulation of renal fibrotic markers, and glomerulosclerosis. rhNRG-1 treatment induced systemic activation of ErbB2 and ErbB4 receptors in both heart and kidneys and prevented LV dilatation, improved LV contractile function, and reduced atherosclerotic plaque size. rhNRG-1 also significantly reduced albuminuria, NGALuria, glomerular fibrosis, and expression of fibrotic markers. Regarding the renal effects of rhNRG-1, further analysis showed that rhNRG-1 inhibited collagen synthesis of glomerular mesangial cells in vitro but did not affect AngII-induced vasoconstriction of glomerular arterioles. In conclusion, systemic administration of rhNRG-1 in hypercholesterolemic type 1 diabetic mice simultaneously protects against complications in the heart, arteries and kidneys.

The state of the hemomicrocirculation system and predictive capacity of parameters characterizing it in patients with hypertensive nephropathy

Today the diagnostics of microcirculatory disorders in patients with hypertensive nephropathy (HN) is an extremely important issue. Aim. To evaluate the functional state of hemomicrocirculatory (HMC) system and to analyze predictive capacity of parameters characterizing it in patients with essential hypertension (EH) of II stage accompanied with manifestations of nephropathy. Methods and results. 155 patients were examined including two main groups of patients with stage II EH of second (n=31) and third (n=31) degree of arterial hypertension (AH) with early signs of nephropathy as well as three comparison groups including patients with essential hypertension stage II of the second (n=31) and third (n=31) degree of hypertension with preserved renal function, and practically healthy individuals (n=31). Albumin/creatinine ratio in urine greater that 30 mg/g was taken as the marker of kidney disorder. The function of HMC system was evaluated by means of laser Doppler flowmetry. It was found that it is typical for patients with HN to show the reduction in tissue perfusion, variability of peripheral blood flow, apparent dysfunctional disorders of the microvascular endothelium, significant neurogenic and myogenic tonus increase. The significant loss of elastic properties of microvessels and pronounced signs of stagnation of blood in the postcapillary segment of microvasculature were also noted. Patients with HN accompanied with the sharp reduction of normocirculatory microcirculation hemodynamic type (HTM) showed increase in the cases of spastic and stagnant-stasis HTM. Conclusions. Among the analyzed parameters which characterize HMC system, A max E and A max C appeared to be the most qualitative predictors of the HN in hypertensive patients and had a joint predictive potential.

Влияние подкожного и внутрижелудочного введения молибдата аммония на водовыделительную и электролитовыделительную функцию почек при экспериментальном гипопаратиреозе

The aim of experiments was to study the effect of hypocalcaemia on renal function changes in&#x0D; intragastric and subcutaneous administration of ammonium molybdate. The experimental hypoparathyroidism&#x0D; was modeled by removal of parathyroid glands in narcotized and immobilized rats by electrotermocauter&#x0D; under thiopental anesthesia. 30 days after the operation calcium concentration in blood was measured&#x0D; and individuals with most severe hypocalcaemia were selected. Ammonium molybdate was introduced&#x0D; intragastrally and subcutaneously at a does of 50 mg |kg daily for 30 days. Studies showed that subcutaneous&#x0D; administration of molybdenum on the background of hypoparathyroidism was associated with more&#x0D; severе renal impairment. Spontaneous urine output increased as a result of the oppression of the relative&#x0D; tubular reabsorption of water, while the glomerular filtration rate decreased. Protein excretion was increased&#x0D; in all groups with the introduction of ammonium molybdate with respect to baseline values, but the most&#x0D; severe proteinuria was noticed in the group with subcutaneous administration of ammonium molybdate in&#x0D; the background parathyroidectomy. Excretion of all studied cations (potassium, sodium, calcium) with urine&#x0D; increased. Histology of the kidneys revealed more pronounced signs of nephropathy.

Choroidal Changes and Duration of Diabetes

Purpose: We investigate changes in macular choroidal thickness in eyes without diabetic retinopathy of patients with various durations of diabetes, using enhanced depth imaging optical coherence tomography (EDI OCT). Methods: The 134 Type-2 diabetic patients who presented without diabetic retinopathy were prospectively imaged using EDI OCT on Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) sd-OCT. The patients with diabetes were classified into three groups, according to the duration of diabetes: Group I (5–9 years, n = 63); Group II (10–14 years, n = 37); Group III (15–40 years, n = 34). The retinal and choroidal thickness was evaluated between these groups at central fovea and at the regions at 500-mm intervals up to 1500 mm temporal and nasal to the fovea. Results: The central foveal retinal thickness was significantly different between groups (group I: 273.05 ± 19.51 µ, group II: 267.12 ± 20.78 µ, group III: 261.34 ± 22.27 µ; p = 0.04). The choroidal thickness measurements at central fovea, at 500, 1000, and 1500 micron intervals temporal and nasal to the center of the fovea were not significantly different between groups. The duration of diabetes was weakly correlated with choroidal thickness in all measured distances and they were not statistically significant. The central foveal choroidal thickness was weakly correlated with serum creatinine (r = −0.18, p = 0.03). Conclusıon: Foveal retinal thickness was significantly decreased in patients with longer duration of diabetes. Duration of diabetes does not seem to be related to foveal chorodial thickness. On the other hand, the weak relation between creatinine and choroidal thickness may be evaluated further. The choroidal thickness changes that may be an early sign of nephropathy can be submitted to an easy, noninvasive scanning test at the same time.