The Role of Sclerostin in Rheumatic Diseases: A Review.

Systemic connective tissue disorders constitute a heterogenous group of autoimmune diseases with the potential to affect a range of organs. Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune inflammatory disease affecting the joints. Systemic lupus erythematosus (SLE) may manifest with multiple system involvement as a result of inflammatory response to autoantibodies. Spondyloarthropathies (SpAs) such as ankylosing spondylitis (AS) or psoriatic arthritis (PsA) are diseases characterised by the inflammation of spinal joints, paraspinal tissues, peripheral joints and enthesitis as well as inflammatory changes in many other systems and organs. Physiologically, sclerostin helps to maintain balance in bone tissue metabolism through the Wnt/ß-catenin pathway, which represents a major intracellular signalling pathway. This review article aims to present the current knowledge on the role of sclerostin in the Wnt/ß-catenin pathway and its correlation with clinical data from RA, SLE, AS and PsA patients.

A Stepwise Screening Protocol for Multiple Myeloma.

BACKGROUND: Monoclonal gammopathies and multiple myeloma should be screened in the primary care setting. METHODS: The screening strategy consisted of an initial interview supported with the analysis of basic laboratory test results and the increasing laboratory workload in the following steps was developed based on characteristics of patients with multiple myeloma. RESULTS: The developed 3-step screening protocol includes evaluation of myeloma-related bone disease, two renal function markers, and three hematologic markers. In the second step, the erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP) were cross-tabulated to identify persons qualifying for confirmation of the presence of monoclonal component. Patients with diagnosed monoclonal gammopathy should be referred to a specialized center to confirm the diagnosis. The screening protocol testing identified 900 patients with increased ESR and normal level of CRP and 94 of them (10.4%) had positive immunofixation. CONCLUSIONS: The proposed screening strategy resulted in an efficient diagnosis of monoclonal gammopathy. The stepwise approach rationalized the diagnostic workload and cost of screening. The protocol would support primary care physicians, standardizing the knowledge about the clinical manifestation of multiple myeloma and the method of evaluation of symptoms and diagnostic test results.

Serum WNT4 protein as an indicator of chronic glomerulonephritis but not a marker of inflammatory cell infiltration and fibrosis: A preliminary study.

BACKGROUND: The WNT signaling pathway contributes to renal fibrosis, which is a hallmark of chronic kidney disease (CKD). Serum concentration of WNT4 could be used to monitor the kidney disease; however, no data have yet been published on the subject. OBJECTIVES: This study measures WNT4 protein in serum of CKD patients depending on the stage, type of nephropathy, the non-nephrotic (NNP) or nephrotic proteinuria (NP), inflammatory cell infiltration in kidney parenchyma (IIKP), interstitial fibrosis in biopsy and serum creatinine. We also evaluated the usefulness of the serum WNT4 as a marker of fibrosis and IIKP. MATERIAL AND METHODS: The WNT4 protein level in serum of CKD patients and healthy individuals was measured using enzyme-linked immunoassay (ELISA). Patients' blood biochemical profiles and kidney biopsies were evaluated with common laboratory methods. RESULTS: The serum level of WNT4 protein was higher in CKD patients (i) regardless of the underlying etiology and at early stages of disease; (ii) with lupus nephritis and Immunoglobulin A (IgA) nephropathy; (iii) without or with a small area of IIKP; and (iv) with a small area covered with fibrosis. No difference was observed between NNP and NP patients. The utility of serum WNT4 as a marker of IIKP and fibrosis was not confirmed. Negative correlations with total and low-density lipoprotein (LDL)-cholesterol were found in CKD and IIKP patients. In patients with serum WNT4 above the median value, serum creatinine was higher. However, no correlation between serum WNT4 and creatinine level was found. CONCLUSIONS: The observed increase in serum WNT4 protein in the early stages of CKD and in patients diagnosed with immune-mediated glomerular disease may suggest that WNT4 may act as a mediator of inflammation. A certain association with the dysregulation of serum lipid metabolism can also be suspected. Serum WNT4 protein may be considered as the indicator of chronic glomerulonephritis, but not a diagnostic marker of IIKP and fibrosis.

What is the prognostic value of reduced eGFR?

Introduction of the definition and classification of chronic kidney disease (CKD) according to the KDOQI guidelines in 2002 served as a turning point in nephrology. On one hand, the new definition has allowed for the standardization of terminology, on the other hand, however, it has led to a rapid growth in CKD diagnoses. Another issue is the strengthening of the assumption, that diagnosis of CKD is associated with further progressive kidney dysfunction until reaching the end stage renal disease (ESRD). Clinical practice, however, provides evidence that not all patients diagnosed with CKD reach ESRD and eventually require renal replacement therapy (RRT), and in many cases CKD does not progress. AIM: The aim of the study was to assess practical information for a clinician provided by eGFR and its changes during the follow-up of a patient as regards the RRT prognosis and mortality risk. MATERIALS AND METHODS: The study group consisted of patients with CKD treated in the regional outpatient clinic. Progression was assessed by determining a linear trend line for eGFR results. Based on its course and the value of the coefficient of determination R2, four types of eGFR trajectories were identified: linear progression type (G2), nonlinear progression type (G1), improvement type (G3), undetermined eGFR change type (G4). RESULTS: The study group consisted of 65 patients 58.5% females, age mean 69 ± 12.8 years. The mean annual eGFR change in the entire group was -1.67±11.7 ml/min/1.73m2/year. During the study, 6.2% of patients began RRT (hemodialysis), and 9.2% died. Despite the evident tendency towards higher mortality in the group characterized by progression (G1+G2) as compared to the group without progression (G3+G4), the difference did not reach statistical significance (p=0.617). However, the comparison of groups with the baseline eGFR value above and below 45 ml/min/1.73 m2 differentiated the two groups that statistically differed in mortality (p=0.044). CONCLUSIONS: The baseline eGFR was not a significant predictor of future renal outcomes (ESRD, RRT). However, eGFR below 45 ml/min/ 1.73m2 was associated with a significantly higher mortality risk (p=0.036). Moreover, the groups with the fastest and with improved eGFR were characterized by the highest mortality.

Pure Red Cell Aplasia and Antibody-Mediated Rejection: Double Trouble in 1 Kidney Transplant Recipient Solved by Intravenous Immunoglobulin Infusion: A Case Report.

Acquired pure red cell aplasia (PRCA) is characterized by severe normocytic (rarely macrocytic) and normochromic anemia, a low reticulocytes count in peripheral blood, and near absence of erythroid precursors in the bone marrow, with a normal level of erythropoietin. We describe a case of the kidney transplant recipient, diagnosed with PRCA induced with parvovirus B19 infection. Our case demonstrates that although this complication is rare, it should be considered in a differential diagnosis of anemia diagnostics in immunocompromised patients. In our case reduced immune response resulted from post-transplant immunosuppressive therapy. In our patient, apart from infection by parvovirus B19, graft dysfunction due to polyomavirus BK virus infection was also detected together with histologic and serologic features of antibody-mediated renal graft rejection. Considering the entire clinical picture, intravenous immunoglobulin therapy (IVIg) was successfully introduced.

Hypertensive kidney disease: a true epidemic or rare disease?

In the industrialized world, hypertension affects approximately 30% of the general population. Hypertensive kidney disease is considered one of the consequences of long-term and poorly controlled hypertension. According to renal databases, it is a leading cause of end­stage renal failure, second only to diabetic kidney disease. We challenge this dogma by emphasizing lack of specificity of both clinical and morphological presentations of hypertension­related kidney disease and very low prevalence of hypertensive kidney disease that is diagnosed based on kidney biopsy findings in registries. In most cases of concomitant hypertension and chronic kidney disease (CKD), the sequence of events (ie, which came first, CKD or hypertension) cannot be established. Arterial hypertension plays a role in the pathogenesis of chronic vascular disease and may occasionally lead to arterionephrosclerosis, but its general significance in the evolution of CKD and prevalence among CKD patients appear to be highly overestimated. Studies of the morphology of kidney biopsies have indicated that arterionephrosclerosis, classically considered a morphological equivalent of the clinical term "hypertensive kidney disease"(previously referred to as "hypertensive nephropathy"), most commonly superimposes upon variable chronic renal diseases, even in the absence of elevated blood pressure. To date, no prospective controlled clinical trials have been conducted in primary hypertension patients with renal events as primary endpoints. Data from available clinical trials with renal events that serve as secondary endpoints suggest that lowering blood pressure below current targets may provide additional cardiovascular benefits but may be harmful to the kidneys.

Versatility of USP18 in physiology and pathophysiology.

Ubiquitin-specific peptidase 18 (USP18) is a multifunctional protein and its roles are still being investigated. This enzyme removes ubiquitin-like molecules from their substrates and the only known interferon-stimulated gene 15 (ISG15) specific protease. Apart from its enzymatic function, it also inhibits interferon type I and III signalling pathways. USP18 is known to regulate multiple processes, such as: cell cycle, cell signalling and response to viral and bacterial infections. Moreover, it contributes to the development of several autoimmune diseases and carcinogenesis, and recently was described as a cardiac remodelling inhibitor. This review summarizes the current knowledge on USP18 functions, highlighting its contribution to the development of heart failure, given the fact that this disease's etiology is now considered to be inflammatory in nature.

WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging.

BACKGROUND/AIMS: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. MATERIALS: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. RESULTS: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. CONCLUSIONS: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.

[Osteoporosis and vascular calcification in rheumatoid arthritis - the role of osteoprotegerin and sclerostin]. / Osteoporoza i kalcyfikacja naczyn w reumatoidalnym zapaleniu stawów ­ rola osteoprotegeryny i sklerostyny.

Disorders of bone tissue metabolism and increased frequency of cardiovascular diseases are among the well-known, extra-articular complications of rheumatoid arthritis (ra). The mechanisms leading to local and generalized loss of bone tissue as well as those promoting calcification of vessels are similar. Recently, a great interest has aroused among the studies related to the meaning of the RANKL/RANK/OPG system and the Wnt/ß-catenin signaling pathway, as biological links between the bone and vascular systems. In the course of ra, lowering of the mineral density of bones and intensification of vascular calcification seem to be associated with the increase of plasma concentration of osteoprotegerin (OPG) and sclerostin - the regulatory proteins of the RANKL/RANK/OPG system and the Wnt/ß-catenin pathway. Molecular mechanisms associated with the osteoblasts' activation and repression of bone resorption in the future can become the target of a precise, combination therapy in osteoporosis and calcification changes. The article presents the role of the RANKL/RANK/ OPG system and the Wnt/ß-catenin pathway in the pathogenesis of disorders of bone tissue metabolism and calcification of vessels in ra, with particular emphasis on the role of OPG and sclerostin.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Kidney disease in the elderly: biopsy based data from 14 renal centers in Poland.

BACKGROUND: Longer life expectancy is associated with an increasing prevalence of kidney disease. Aging itself may cause renal damage, but the spectrum of kidney disorders that affect elderly patients is diverse. Few studies, mostly form US, Asia and West Europe found differences in the prevalence of some types of kidney diseases between elderly and younger patients based on renal biopsy findings, with varied proportion between glomerulopathies and arterionephrosclerosis as a dominant injury found. Here, for the first time in Eastern Europe we analyzed native kidney biopsy findings and their relationship to clinical characteristics at the time of biopsy in elderly individuals (aged ≥65) in comparison to younger adults (aged 18-64). METHODS: Biopsy and clinical data from 352 patients aged ≥65 were retrospectively identified, analyzed and compared with a control group of 2214 individuals aged 18-64. All kidney biopsies studied were examined at Medical University of Warsaw in years 2009-14. RESULTS: In elderly patients the leading indication for biopsy was nephrotic range proteinuria without hematuria (34.2%) and the most prevalent pathologic diagnoses were: membranous glomerulonephritis (MGN) (18.2%), focal segmental glomerulosclerosis (FSGS) (17.3%) amyloidosis (13.9%) and pauci immune glomerulonephritis (12.8%). Hypertension and age-related lesions very rarely were found an exclusive or dominant finding in a kidney biopsy (1.7%) and a cause of proteinuria (1.1%) in elderly individuals. There were 18.2% diabetics among elderly individuals, and as much as 75% of them had no morphologic signs of diabetic kidney disease in the renal biopsy. Amyloidosis, MGN, pauci immune GN, crescentic GN and light and/or heavy chain deposition disease (LCDD/HCDD) were more frequent whereas IgA nephropathy (IgAN), lupus nephritis (LN) and thin basement membrane disease (TBMD) were less common among elderly than in younger patients. CONCLUSIONS: Proteinuria, a dominating manifestation in elderly patients subjected to kidney biopsy was most commonly related to glomerulopathies. The relatively high prevalence of potentially curative kidney diseases in elderly individuals implicates the importance of renal biopsy in these patients.

[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age]. / Rekomendacje dotyczace profilaktyki pozaszpitalnego zapalenia pluc z bakteriemia jako wiodacej postaci inwazyjnych zakazen pneumokokowych w populacji osób powyzej 50 roku zycia oraz w grupach ryzyka powyzej 19 roku zycia.

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.

Unusual manifestation of crystalline light chain tubulopathy in patient with multiple myeloma: case report and review of the literature.

Multiple myeloma (MM) is the second most common hematological malignancy, with an annual incidence in Europe and the USA of about 4-6 cases per 100,000. Several forms of renal disease are found in the course of MM, including: cast nephropathy, light chain (LC) deposition disease and primary amyloidosis. Less frequent forms include: acute and chronic tubulopathies, neoplastic plasma cell infiltration and interstitial nephritis. In this paper, we discuss a case of 53-year-old male patient with MM who presented with massive proteinuria (24 g/24 h), mild renal insufficiency (eGFR 43 mL/min), and Fanconi-like syndrome (as reflected by normoglycemic glycosuria). In kidney biopsy glomeruli were normal, whereas abundant AFOG-positive deposits were found in the cytoplasm of proximal tubular epithelial cells. These deposits were strongly positive for kappa light chains on immunofluorescence. Electron microscopy revealed electron-dense, intracytoplasmic crystalloid deposits of variable shape (needle-shaped, round and rectangular), and size in the proximal tubular cells. This unusual variant of microscopic renal lesions in the course of MM coupled with coincidence of Fanconi-like and nephrotic syndrome as a clinical manifestation has not been reported to date.

Renal involvement in multiple myeloma.

In this paper, the spectrum of renal involvement in the course of multiple myeloma (MM) is discussed. We describe the most important pathophysiological mechanisms underlying the development of renal complications observed in MM. In particular, we focused on the correlations between morphological changes in the kidneys and clinical signs and symptoms. Physicochemical characteristics of light chains that are synthesized in excess are critically important in the development of different types of renal involvement. It seems that patients with MM should be actively treated regardless of the type of lesions because the current methods allow to reverse renal lesions and reduce the negative effect of renal damage on prognosis in these patients.

Identifying chronic kidney disease in an emergency department: a chance for an early diagnosis.

INTRODUCTION: Chronic kidney disease (CKD) has relatively asymptomatic course, but even at its onset, it worsens the prognosis of patients, mainly because of the increased risk of cardiovascular diseases. Several population-based screening programs as well as initiatives focused on certain risk groups were undertaken to better diagnose early stages of CKD. It appears that an emergency department (ED) of a hospital may be the right place to screen for early CKD. OBJECTIVES: The aim of the study was to assess the accuracy of ED practices in the detection of CKD. PATIENTS AND METHODS: The study involved 176 subjects who presented at the ED over 1 month and were subsequently admitted to one of the wards at the general hospital. Blood pressure on admission was recorded in 61% of the patients; serum creatinine and estimated glomerular filtration rate (eGFR) were measured in 50% of the subjects, urea in 42.2%, potassium in 87.5%, and glucose in 82%. Patients with previously diagnosed CKD were excluded from the study. RESULTS: Sixty-three per cent of blood pressure values exceeded 140/90 mmHg, 27.3% of all creatinine samples exceeded the upper limit of 1.2 mg/dl, and 64.8% of eGFR results were below 90 ml/min/1.73 m² (mean 78 ± 36 ml/min/1.73 m²). Abnormal levels of urea (>50 mg/dl) were observed in 32% of the patients. Potassium levels were within the reference range in 81.5% of the patients (3.5-5.0 mmol/l; only 10.4% exceeding 5 mmol/l). Elevated glucose levels (>110 mg/dl) were observed in 60% of the patients. CONCLUSIONS: ED practices could be used to identify a significant number of patients with undiagnosed CKD. However, these simple, widely available, and cost-effective methods of early CKD detection are underused. Our results show that there is an urgent need for a structural screening program for CKD at the level of ED.

Renal artery stenosis in patients with coronary artery disease.

BACKGROUND: Renal dysfunction is an important factor of cardiovascular risk. Renal artery stenosis (RAS) is a potential cause of secondary hypertension and by renal ischemia may lead to progressive renal insuficiency. In RAS patients a significant increase in prevalence of coronary artery disease (CAD) as well as revascularisation rate and mortality rate was observed. AIM: To determine the prevalence of RAS in patients with suspected CAD. METHODS: The study group consisted of 1036 consecutive patients (700 men; 67.6% ) in the mean age of 62.1+/-9.7 (25-85) years admitted to coronary angiography. Simultaneously renal angiography was performed in all patients. RESULTS: Stenosis > or = 50% in at least one main branch of coronary artery was found in 633 (66.1%) patients. The proportion of patients with one, two or three vessel CAD was respectively 291 (46%), 169 (26%) and 173 (27.3%). Non-significant coronary lesions <50% were found in 108 (10.4%) patients, whereas in 295 (28.5%) patients no angiographic evidence of CAD was documented. In the whole group of patients RAS was found in 339 (32.7%) of patients - 124 (12%) had bilateral lesions. RAS prevalence in patients with CAD was 38.3% (284/741) and its frequency increased with severity of CAD: from 25% (27/108) in patients with insignificant coronary lesions up to 36.4% (106/291), 40.2% (68/169) and 48% (83/173) in 1, 2, and 3-vessel disease, respectively (p <0.001). RAS prevalence in patients with normal coronary arteries was 18.6% (55/295). RAS <30% was detected in 194 (18,7%) patients; RAS between 30-49% in 81 patients (8.7%); RAS 50-69% in 38 patients (3.7%) and RAS > or = 70% in the remaining 26 patients (2.5%). RAS > or = 50% was noted in 8 (2.7%) patients without coronary lesions; in 5 (4.6%) with insignificant coronary artery atherosclerosis and 51 (8%) with coronary artery stenosis >50% (p=0.0008). Stepwise regression analysis identified 4 independent predictors of RAS > or = 50%: CAD severity (p=0.014), serum creatinine concentration (p <0.001), cigarette smoking (p=0.02) and stenosis of aortic arch branches (p <0.001). CONCLUSIONS: RAS is a frequent finding in patients with suspected CAD. CAD severity, number of involved aortic arch arteries, cigarette smoking and serum creatinine are independent RAS predictors.

An overview of the pathophysiology of vascular calcification in chronic kidney disease.

Abnormalities of calcium-phosphate balance, with subsequent bone metabolism disorders, are among the key and earliest features of chronic kidney disease (CKD). Recently, another consequence of these abnormalities was brought to light-namely, vascular calcification. Most studies performed in patients on dialysis suggest that their vascular calcification is more advanced than that seen in the general population. Furthermore, the progression of vessel wall mineralization is much more dynamic in patients with CKD. Apart from the commonly assessed factors that promote vascular calcification, such as age, duration of dialysis, or poor control of calcium-phosphate status, several other factors have recently been identified. In the spectrum of substances involved in the regulation of the process of soft-tissue calcification, the most extensively studied in the nephrology literature are bone morphogenetic protein 7, osteoprotegerin, matrix Gla protein, fetuin-A, and the phosphatonins. Better understanding of the mechanisms underlying excess vascular mineralization have led to the development of promising new therapies.

Does coronary artery calcification in patients with diabetic nephropathy depend on the advancement of renal failure?

Calcium-phosphate disorders and vascular calcification are highly prevalent in patients with diabetes mellitus and nephropathy. The aim of the study was to compare the prevalence and advancement of vascular calcification in patients with end-stage diabetic nephropathy on peritoneal dialysis and diabetic patients with chronic renal disease stages 2-4. The study group included 31 patients with type 2 diabetes and diabetic nephropathy divided into 2 groups: 12 patients (aged 50-74 years: mean 58.6+/-8.8) undergoing peritoneal dialysis and 19 patients (aged 46-82 years; mean 65.8+/-9.7) with chronic kidney disease stages 2-4 (GFR range 24-78 ml/min/1.73 m2). Coronary artery calcification score, was assessed using multi-slice computed tomography. Coronary artery calcification score did not differ significantly between groups (CaSc values 1085.2 vs 452.4 AgU; NS). The patients undergoing peritoneal dialysis showed significantly higher levels of parathyroid hormone (658.2 vs. 74.3 pg/ml; p=0.001), fibrinogen (5.82 vs. 3.89 g/l; p<0.0001) and alkaline phosphatase (330.9 vs. 168.0 U/l; p=0.001). Despite more advanced abnormalities in calcium-phosphate balance parameters and more active inflammation in peritoneal dialysis subjects we failed to demonstrate any statistically significant difference in coronary artery calcification score between patients with diabetic nephropathy on peritoneal dialysis and those with chronic kidney disease stages 2-4.