[Experience with active vitamin D metabolites in phosphorus-calcium metabolic disorders in patients with predialysis chronic kidney disease].

AIM: To evaluate the efficacy and safety of alfacalcidol and paracalcitol used to correct impaired phosphorus-calcium metabolism (PCM) in patients with predialysis chronic kidney disease (CKD). SUBJECTS AND METHODS: Examinations were made in 128 patients with Stages III-V CKD, including 89 (69.5%) patients with chronic glomerulonephritis, 30 (23.4%) with chronic tubulointerstitial nephritis, and 9 (7.1%) with hypertensive nephrosclerosis. Impaired PCM was detected in 90 (70.3%) of the examined patients. According to the pattern of the previous therapy, all the 90 CKD patients with PCM disorders were divided into 3 groups: 1) 32 patients with Stages IIIB-V CKD who had taken oral alfacalcidol 0.25 microg/day; 2) 28 patients with Stages IIIB-V CKD who had used oral paricalcitol 1 microg/day; 3) 30 patients with Stages IIIB-V CKD who had not received, as self- motivated, active vitamin D metabolites at the predialysis stage. RESULTS: Alfacalcidol and paricalcitol were quite satisfactorily tolerated by the patients. After 3 months of initiation of the use of these agents, Groups 1 and 2 patients with predialysis CKD and baseline elevated blood intact parathyroid hormone (iPTH) levels could not only achieve, but also maintain target blood iPTH levels. In the patients taking paricalcitol, the urinary protein level decreased more promptly; moreover, by the end of month 6 the reduction in blood pressure (BP) was more significant than in those using alfacalcidol (p < 0.05). Comparison of the effects of angiotensin-converting enzyme inhibitors in combination with alfacalcidol or paricalcitol on BP changes and left ventricular mass index indicated that the most pronounced positive changes occurred when angiotensin-converting enzyme inhibitors were used in combination with paricalcitol. CONCLUSION: The use of paricalcitol in predialysis CKD with PTH hyperproduction results in not only normalization of the levels of both PTH and osseous isoenzyme of alkaline phosphatase, but also in significantly reduced daily proteinuria and regression of left ventricular hypertrophy and chronic heart failure.

[Significance of the morphogenetic proteins FGF-23 and Klotho as predictors of prognosis of chronic kidney disease].

AIM: To study the role of the morphogenetic proteins FGF-23 and Klotho in the progression of chronic kidney disease (CKD) and in the development of cardiovascular events, inflammation, protein-energy deficiency, and other complications. SUBJECTS AND METHODS: Examinations were made in 70 patients with Stages I-VD CKD: 41 with chronic glomerulonephritis (including 10 with nephritis in the presence of diffuse connective tissue diseases), 22 with tubulointerstitial nephritis, and 7 with hypertensive nephrosclerosis. There were a total of 30 men and 40 women whose age was 20 to 84 years; the mean age at the study inclusion was 41 +/- 6.7 years. The serum levels of FGF-23 (Human FGF-23 ELISA kit using monoclonal antibodies to complete molecule of FGF-23) and Klotho (Human alpha-K1 ELISA using anti-Klotho antibodies) were investigated in all the 70 patients with CKD. RESULTS: The sera of all the examinees with CKD showed elevated FGF-23 and decreased Klotho levels, the magnitude of a change in which increased from Stage I to VD. In patients with different stages of CKD, the increase in FGF-23 levels, as glomerular filtration rate reduced, outstripped that in the serum levels of phosphorus and intact parathyroid hormone. There was a strong correlation of the serum level of the morphogenetic proteins, Klotho in particular, with proteinuria, C-reactive protein level, protein-energy deficiency, indicating the pleiotropic effects of these proteins. There was also a strong correlation between serum Klotho and ferritin levels and transferrin saturation percentage, which suggests that Klotho may be involved in iron regulation. CONCLUSION: The results of the investigation lend credence to the experimental and clinical findings that the serum levels of the morphogenetic proteins FGF-23 (an increase) and Klotho (a decrease) are early markers for progressive CKD and that their changes begin just in Stage III CKD and progress as renal failure worsens.

[New markers of cardio-renal links in chronic kidney disease].

AIM: To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD). SUBJECTS AND METHODS: The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol. RESULTS: As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01 and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01, respectively). The same strong association was found between the higher serum level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = -0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study). CONCLUSION: Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).

[Long-acting erythropoetin efficacy in the treatment of nephrogenic anemia in patients with chronic kidney disease during predialysis stage].

AIM: Comparison of efficacy of 12-month treatment of anemia in patients with chronic kidney disease (CKD) of stage III - IV with a long-acting drug darbepoetin alpha - aranesp and short-acting drug erythropoietin beta - recormon. MATERIAL AND METHODS: A total of 44 patients with CKD of stage III-IVwere divided into two groups. Of them, 24 had chronic glomerulonephritis and 20 had tubulointerstitial nephritis with verified nephrogenic anemia. Group 1 consisted of 22 patients given long-acting erythropoetin (darbepoetin alpha) in an initial dose 0,75 mcg/kg each 2 weeks subcutaneously. Group 2 consisted of 22 patients matched by age, gender, severity of anemia and renal failure with group 1 patients given short-acting erythropoietin (erythropoietin beta) in an initial 20 IU 3 times a week subcutaneous, for 12 months. In the phase of anemia correction and supporting therapy the levels of packed red blood cells, Hb, free serum ferrum, ferritin, percentage of iron in transfusion, serum albumin in blood serum, creatinin, glomerular filtration rate were examined monthly. The patients themselves daily measured blood pressure, diuresis, body mass. RESULTS: The target level of Hb 110-120 g/l was achieved faster in group 2 than in group 1 (3 and 4 months, respectively). p < 0.05). In the phase of supporting a target Hb level, on the opposite, darbepoetin alpha provided more stable hemopoetin effect than erythropoietin beta, darbepoetin alpha median dose being constant in the course of the study.

[The role of D2 vitamin metabolite paricalcitol in nephroprotective strategy in chronic disease of the kidneys].

Calcitriol is important in nephroprotective strategy in chronic disease of the kidneys (CDK). However, its long-term use often results in hypercalciemia with metastatic calcification. Compared to calcitriol, paricalcitol (zemplar)--metabolite of vitamin D2--leads to hypercalciemia less frequently, has a more potent nephroprotective effect and more rapidly decreases blood levels of parathyroid hormone. Paricalcitol in combination with lozartan has more pronounced nephroprotective effect. Morphological analysis detected inhibition of development of glomerulosclerosis and tubulointerstitial fibrosis. A cardioprotective effect of paricalcitol manifests with reduction of mortality from cardiovascular complications both at CDKpredialysis stage and in regular hemodialysis.

[Mechanisms of phosphorus and calcium homeostatic disorders in the development of cardiovascular events in patients with chronic renal diseases. The role of fibroblast growth factor 23 and Klotho].

The paper deals with the analysis of studies of the role of the bone morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klothno in the development of vascular wall calcification in chronic renal disease (CRD). FGF-23 is shown to be an important phosphaturic hormone that inhibits hypercalcemic and hyperphosphatemic effects of elevated serum vitamin D concentrations. There is evidence that there is an association between high serum FGF-23 levels and vascular wall calcification irrespective of the content of phosphorus and parathyroid hormone. Most authors regard FGF-23 as a potential uremic toxin in patients with end-stage CRD. There are data that support the renoprotective value of the morphogenetic protein Klotho whose expression in CRD is decreased.

[The role of balanced low-protein diet in inhibition of predialysis chronic kidney disease progression in patients with systemic diseases].

AIM: To evaluate the effects of low-protein diet (LPD) balanced by addition of highly energetic mix and essential keto/amino acids on inhibition of renal failure in patients with systemic diseases with predialysis stages of chronic disease of the kidney (CDK). MATERIAL AND METHODS: Forty six patients with stage III--IV of CDK in systemic diseases (33 SLE patients and 13 with systemic vasculitis) were randomized into three groups. Group 1 consisted of 18 patients with CDK (10 with stage III and 8 with stage IV). They received LPD (0.6 g/kg/day) with addition of essential keto/amino acids for 24-48 months. Group 2 of 18 CDK patients with the same stages received the same diet but greater amount of vegetable protein (highly purified soya protein) to 0.3 g/kg/day in highly energetic nutrient mixture. Group 3--10 CDK patients (7 with stage III and 3 with stage IV) received free diet. Group 1 and 2 patients received LPD irrespective of the nutrient status assessed basing on anthropometric and other data. Protein consumption and caloric value were estimated by 3-day food diary. RESULTS: Before diet therapy, out of 46 examinees nutrient status was abnormal in 45.7% patients. Both variants of LPD were well tolerated and nutrient status was corrected while the rate of nutritive disorders in group 3 increased 1.5-fold (from 40 to 60%) with progression of renal failure. Intake of LPD diet for at least a year reduced glomerular filtration rate inhibition, especially in addition of highly energetic mixture. CONCLUSION: Early (predialysis) restriction of diet protein (0.6 g/kg/day) with addition of highly energetic mixture and essential keto/amino acids improves a nutritive status of CDK patients and inhibits GFR decline.

[Nephroprotective role of early correction of impaired nutritional status in patients with chronic disease of the kidneys at a predialysis stage].

AIM: To assess the rate and clinical significance of impaired nutritional status and impact of low-protein diet on inhibition of renal insufficiency in patients of stage III-IV chronic disease of the kidneys (CDK). MATERIAL AND METHODS: A total of 200 patients with CDK stage III-IV were randomized into three groups: group 1 consisted of 123 patients with chronic glomerulonephritis (73 with stage III and 50 with stage 1V), group 2--45 patients with systemic diseases (30 with stage III and 15 with stage IV), group 3 (a comparison group)--32 patients with CGN (17 with stage 111 and 15 with stage IV). Patients of groups 1 and 2 received low-protein diet (0.6 g protein kg/day) balanced by either high-calorie mix containing protein SUPRO 760 or ketosteril for 24-48 months. The nutritional status was studied by anthropometric data, absolute number of lymphocytes, levels of blood albumin and transferring, intake of protein, food calorie value according to 3-day diaries. RESULTS: Among 200 patients impaired nutritional status was detected in 22 (11.0%) patients. More than half of them had glomerulonephritis in systemic diseases (SLE, systemic vasculitis). Only in patients with systemic diseases nutritional disorders manifested at stage III. These disorders grew with progression of renal insufficiency and were detected primarily in patients with stage IV CDK. Patients with CGN on low-protein diet for a year and longer demonstrated slowing of the fall of the glomerular filtration rate (GFR). CONCLUSION: Early (predialysis) use of low-protein diet balanced by addition of amino- and keto-acids and high-energy nutritional mixes has a positive influence on nutritional status of patients with chronic renal insufficiency and can inhibit GFR lowering.

[Erythropoetin and iron preparations in the treatment of anemia in patients with chronic kidney disease of stage III-IV in systemic diseases].

AIM: To study efficacy and safety of long-term administration of epoetin and iron preparations in glomerulonephritis (GN) patients with chronic kidney disease (CKD) of stage III-IV in systemic diseases. MATERIAL AND METHODS: A total of 189 patients at predialysis stage of CKD (glomerular filtration rate between 15 and 60 ml/min) were randomized into 3 groups depending on GN etiology: primary GN (group 1, 123 patients), GN in systemic diseases (group 2, 45 patients), controls (group 3, 21 patients). Anemia was characterized not only by red cells indices but also by the level of serum ferritin, C-reactive protein (CRP), saturation of transferrin with iron. Remodeling of the heart was determined in all the patients at dopplerechocardiography estimating left ventricular myocardial mass, relative thickness of its wall. RESULTS: Correction of anemia was achieved in all the patients with GN and CKD of stage III-IV in systemic diseases despite the activity of systemic disease (high blood level of CRP) and persistent nephritis activity (high proteinuria). In many patients from groups 1 and 2 who were initially diagnosed to have left ventricular hypertrophy (LVH) of excentric type LVH regressed after 6 months of anemia correction. In group 3 with untreated anemia frequency of LVH increased. CONCLUSION: Treatment of anemia in GN patients with CKD of stage III-IV in systemic diseases needed higher doses of epoetin and parenteral iron preparations compared to patients with the above stages of CKD with primary GN.

[Calcification of peripheral arteries in patients with terminal renal failure on programmed hemodialysis].

AIM: To estimate incidence and clinical significance of carotid and femoral arteries calcification in patients with terminal renal failure (TRF) on programmed hemodialysis (PH). MATERIAL AND METHODS: Thirty four patients (25 males and 9 females) with TRF were divided into two groups by severity of hyperphosphatemia: 15 patients with P < 6 mg/dl (group 1) and 19 patients with P > 6 mg/dl. The groups were matched by age (44.4 +/- 15.05 and 42.7 +/- 14.23 years, respectively) and PH duration (2.4 +/- 1.1 and 2.6 +/- 1.16 years, respectively). Calcification of the arteries and structure of the vascular wall were examined with ultrasonic dopplerography of the common carotid and femoral arteries. Measurements were made of intima-media complex (IMC) thickness, systolic and diastolic diameter of the right and left carotid artery. The arteries were studied for the presence of calcinates and atherosclerotic plaques. RESULTS: Patients of group 2 showed a correlation between a P level, incidence rate of common carotid arteries calcification, atherosclerotic plaques in the femoral arteries, IMC of the carotid and femoral arteries, left ventricular hypertrophy and a decline in a left ventricular diastolic function. A significant correlation was established between the rate of atherosclerotic plaques detection and age, male sex, smoking and history of PH. An increase in IMC and arterial rigidity was revealed in 12 (63.2%) of 19 patients of group 2. They had episodes of intradialysis hypotonia, 6 (31.6%) patients had acute coronary syndrome, 5 (26.3%) patients--cardiac arrhythmia. CONCLUSION: A significant contribution to formation of risk factors of cardiovascular complications in TRF patients on PH is made by disturbed phosphorus-calcium metabolism resulting in higher rigidity and diameter of the arteries. The above changes lead to a rise in systolic pressure and fall in diastolic one. Increased pulse pressure is an independent predictor of the risk to develop acute coronary syndrome.

[Cardioprotective effect of erythropoietin preparations in patients with chronic renal failure]. / Kardioprotektivnyi éffekt preparatov éritropoétina u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

AIM: To investigate effects of early correction of anemia on the rate of cardiovascular complications and survival on regular hemodialysis (RHD). MATERIAL AND METHODS: Eighty patients with chronic renal failure (CRF) on regular hemodialysis entered two groups: group 1 with hemoglobin (Hb) < 80 g/l (n = 36) and group 2 with Hb > 100 g/l (n = 44). 90% patients of group 2 were treated for renal anemia for 6-8 months of predialysis CRF. When placed on RHD, group 1 started therapy with epoetin, 39 patients of group 2 continued epoetin treatment. RESULTS: Patients of group 2 had a higher rate of eccentric left ventricular hypertrophy (LVH) with reduced ejection fraction and development of congestive cardiac failure and coronary heart disease. Eccentric LVH in group 1 patients regressed only in 80% when the patients were on hemodialysis and received epoetin for correction of anemia. Overall cardiac death in group 1 was twice that of group 2 patients. CONCLUSION: Early correction of anemia led to a 50% increase in 5-year survival. This fact can be explained with inhibited progression of eccentric LVH.

[Intradialysis hypotension: causes and sequelae]. / Intradializnaia gipotoniia: ee prichiny i posledstviia.

AIM: To study causes and sequelae of intradialysis hypotension (IH) in patients with terminal renal failure (TRF). MATERIAL AND METHODS: Forty one patients with TRF on chronic hemodialysis (CH) were divided into two groups. The study group consisted of 24 patients with episodes of IH. Seventeen patients of the control group had no IH. All the patients were examined with assessment of protein-energy deficiency, residual renal function, left-ventricular hypertrophy, diastolic function of the heart. Hemodialysis effectiveness was estimated by Kt/V index. Survival of the patients was calculated according to Kaplan-Meier method. RESULTS: In the study group IH episodes occurred in spite of low ultrafiltration velocity (8-10 ml/min). Those patients of the study group who had IH associated with polyneuropathy and left-ventricular hypertrophy had IH episodes more often and sharper falls of arterial pressure. Long-term IH decreased survival significantly. CONCLUSION: Repeated episodes of IH deteriorate effectiveness of hemodialysis because of acute coronary syndrome, acute disorder of cerebral circulation, complications of deficient dialysis syndrome (pericarditis, hyperkaliemia, pulmonary edema, congestive heart failure).

[Prognostic significance of controlled and uncontrolled arterial hypertension in patients with terminal kidney failure on chronic hemodialysis]. / Prognosticheskoe znachenie kontroliruemoi i nekontroliruemoi arterial'noi gipertonii u bol'nykh s terminal'noi pochechnoi nedostatochnost'iu, nakhodiashchikhsia na khronicheskom gemodialize.

AIM: To assess prognostic implications of controlled and uncontrolled arterial hypertension (AH) in patients with terminal renal failure (TRF) on chronic hemodialysis (CHD). MATERIAL AND METHODS: 90 patients on CHD treated from 1981 to 2001 participated in the trial. All of them were examined morphologically (biopsy of the kidney or autopsy). According to the trend of arterial pressure during CHD treatment they were divided into 3 groups. 72 patients of group 1 had sodium-dependent AH. 8 patients of group 2 had uncontrollable AH (rise of arterial pressure during hemodialysis in spite of controlled iltrafiltration). Group 3 consisted of control patients. RESULTS: It was found that any hypertension in CHD patients is prognostically unfavourable. Controllable AH occurred in 91.1%, uncontrollable--in 8.9% of examinees. Chronic renal failure in 20% of group 1 patients was associated with rapidly progressive nephritis, in 15%--with systemic vasculitides. In group 2, 38% patients had systemic vasculitis, 50%--rapidly progressive nephritis. The activity of the underlying disease in hemodialysis was registered in 75 and 30% patients of group 2 and 1, respectively. Incomplete dialysis syndrome (IDS) was diagnosed in 69.6% group 1 and 40.0% group 2 patients. CONCLUSION: Sodium dependent arterial hypertension was most frequent. It is attributed to IDS. AH uncontrolled by hemodialysis develops, as a rule, in patients with systemic vasculitis or active primary nephritis. Uncontrollable AH is characterized by elevated plasm renin. Lack of control over arterial pressure in hemodialysis is essential for long-term survival of the patients. The shortest survival was observed in patients with renin-dependent AH. Factors provoking AH and deteriorating the prognosis are the following: hypervolemia in IDS, hyperactivity of plasm renin, exacerbation of basic disease in hemodialysis, protein energy deficiency syndrome, lack of residual renal function.

[Treatment of bone disorders in renal diseases]. / Lechenie patologii kostnoi sistemy pri zabolevaniiakh pochek.

AIM: To study possible correction of bone disorders (osteopenia, Ca/P-imbalance, bone pain, limited volume of indolent movements) which are still a serious complication associated with renal diseases and pathogenic therapy (steroids). MATERIALS AND METHODS: The bone disorders were treated in 10 uremic hemodialyzed patients (8 men, 2 women; group 1) with vitamin D3 (calcitriol made in Russia) + rhEPO (recormon; Boehringer Mannheim), in 15 patients (15 women, 0 men) with lupus-nephritis (group 2) with vitamin D3 (n = 5, group 2a) or miscalcic (Sandoz) (n = 10, group 2b), in 2 patients (2 men, 0 women) with glomerulonephritis (group 3) with vitamin D3 + miacalcic. Additionally all the patients received Ca salts. In groups 2 and 3 renal function was normal. The duration of the treatment was 3-6 months. RESULTS: In all the groups we obtained an analgetic effect (attenuation of bone pain and more indolent movements), improvement of life quality, diminished need in analgetics, elevation of serum Ca level (p > 0.05). CONCLUSION: Treatment of renal patients with bone affection with vitamin D3 and miacalcic has an analgetic effect, improves life quality.