Hepatocyte Nuclear Factor-1α Increases Fibrinogen Gene Expression in Liver and Plasma Fibrinogen Concentration in Rats with Experimental Chronic Renal Failure.

Chronic kidney disease (CKD) is associated with elevated plasma fibrinogen concentration. However, the underlying molecular mechanism for elevated plasma fibrinogen concentration in CKD patients has not yet been clarified. We recently found that HNF1α was significantly upregulated in the liver of chronic renal failure (CRF) rats, an experimental model of CKD in patients. Given that the promoter region of the fibrinogen gene possesses potential binding sites for HNF1α, we hypothesized that the upregulation of HNF1α can increase fibrinogen gene expression and consequently plasma fibrinogen concentration in the experimental model of CKD. Here, we found the coordinated upregulation of Aα-chain fibrinogen and Hnfα gene expression in the liver and elevated plasma fibrinogen concentrations in CRF rats, compared with pair-fed and control animals. Liver Aα-chain fibrinogen and HNF1α mRNAs levels correlated positively with (a) liver and plasma fibrinogen levels and (b) liver HNF1α protein levels. The positive correlation between (a) liver Aα-chain fibrinogen mRNA level, (b) liver Aα-chain fibrinogen level, and (c) serum markers of renal function suggest that fibrinogen gene transcription is closely related to the progression of kidney disease. Knockdown of Hnfα in the HepG2 cell line by small interfering RNA (siRNA) led to a decrease in fibrinogen mRNA levels. Clofibrate, an anti-lipidemic drug that reduces plasma fibrinogen concentration in humans, decreased both HNF1α and Aα-chain fibrinogen mRNAs levels in (a) the liver of CRF rats and (b) HepG2 cells. The obtained results suggest that (a) an elevated level of liver HNF1α can play an important role in the upregulation of fibrinogen gene expression in the liver of CRF rats, leading to an elevated concentration of plasma fibrinogen, a protein related to the risk of cardiovascular disease in CKD patients, and (b) fibrates can decrease plasma fibrinogen concentration through inhibition of HNF1α gene expression.

Hepatocyte Nuclear Factor 1α Proinflammatory Effect Linked to the Overexpression of Liver Nuclear Factor-κB in Experimental Model of Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with low-grade inflammation that activates nuclear factor-κB (NF-κB), which upregulates the expression of numerous NF-κB responsive genes, including the genes encoding IL-6, ICAM-1, VCAM-1, and MCP-1. Herein, we found the coordinated overexpression of genes encoding RelA/p65 (a subunit of NF-κB) and HNF1α in the livers of chronic renal failure (CRF) rats-an experimental model of CKD. The coordinated overexpression of RelA/p65 and HNF1α was associated with a significant increase in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. A positive correlation between liver RelA/p65 mRNA levels and a serum concentration of creatinine and BUN suggest that RelA/p65 gene transcription is tightly related to the progression of renal failure. The knockdown of HNF1α in the HepG2 cell line by siRNA led to a decrease in Rel A/p65 mRNA levels. This was associated with a decrease in IL-6, ICAM-1, VCAM-1, and MCP-1 gene expressions. The simultaneous repression of HNF-1α and RelA/p65 by clofibrate is tightly associated with the downregulation of IL-6, ICAM-1, VCAM-1, and MCP-1 gene expression. In conclusion, our findings suggest that NF-κB could be a downstream component of the HNF1α-initiated signaling pathway in the livers of CRF rats.

Locking Hemodialysis Catheters With Trimethoprim-Ethanol-Ca-EDTA to Prevent Bloodstream Infections: A Randomized, Evaluator-blinded Clinical Trial.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) often result from intraluminal microbial colonization and are associated with morbidity, mortality, and substantial costs. The use of antimicrobial catheter lock solutions may reduce the incidence of CLABSI. METHODS: Patients undergoing hemodialysis (HD) through a prevalent central venous catheter (CVC) were randomly assigned to have their CVC locked between dialysis sessions with an antimicrobial catheter lock solution that contained trimethoprim 5 mg/mL, ethanol 25%, and Ca-EDTA 3% (investigational medical device [IMD]) or heparin 5000 U/mL active control heparin (ACH). Exit site care was standardized by protocol-driven use of skin antiseptics and occlusive dressings. The composite primary endpoint consisted of the incidence of CLABSI and intracatheter thrombolytic treatment (TT). Given the viscosity and odor of the IMD, blinding was impossible. Therefore, a blinded endpoint committee adjudicated the incidence of CLABSI. RESULTS: A total of 270 patients on HD were enrolled and followed for 43738 CVC-days. Despite the low CLABSI incidence of 0.41/1000 CVC-days in patients randomized to ACH, the IMD further reduced the incidence 4.56-fold to 0.09/1000 CVC-days (P < .03). The product was well tolerated, and the frequency and severity of adverse events were comparable between groups. Intracatheter instillation of thrombolytics was more frequent in patients who received the IMD (12% ACH, 40% IMD; P < .001), but rates of catheter removal did not differ (13% ACH, 11% IMD). Overall, dialysis adequacy was comparable between groups. CONCLUSIONS: In patients on chronic HD, a trimethoprim, ethanol, and Ca-EDTA lock solution significantly reduced the incidence of CLABSI. CLINICAL TRIALS REGISTRATION: NCT01989091.

Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study.

BACKGROUND: Serum phosphate is a key parameter in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). The timing of phosphate measurement is not standardized in the current guidelines. Since the optimal range of these biomarkers may vary depending on the duration of the interdialytic interval, in this analysis of the Current management of secondary hyperparathyroidism: a multicentre observational study (COSMOS), we assessed the influence of a 2- (midweek) or 3-day (post-weekend) dialysis interval for blood withdrawal on serum levels of CKD-MBD biomarkers and their association with mortality risk. METHODS: The COSMOS cohort (6797 patients, CKD Stage 5D) was divided into two groups depending upon midweek or post-weekend blood collection. Univariate and multivariate Cox's models adjusted hazard ratios (HRs) by demographics and comorbidities, treatments and biochemical parameters from a patient/centre database collected at baseline and every 6 months for 3 years. RESULTS: There were no differences in serum calcium or parathyroid hormone levels between midweek and post-weekend patients. However, in post-weekend patients, the mean serum phosphate levels were higher compared with midweek patients (5.5 ± 1.4 versus 5.2 ± 1.4 mg/dL, P < 0.001). Also, the range of serum phosphate with the lowest mortality risk [HR ≤ 1.1; midweek: 3.5-4.9 mg/dL (95% confidence interval, CI: 2.9-5.2 mg/dL); post-weekend: 3.8-5.7 mg/dL (95% CI: 3.0-6.4 mg/dL)] showed significant differences in the upper limit (P = 0.021). CONCLUSION: Midweek and post-weekend serum phosphate levels and their target ranges associated with the lowest mortality risk differ. Thus, clinical guidelines should consider the timing of blood withdrawal when recommending optimal target ranges for serum phosphate and therapeutic strategies for phosphate control.

Impact of donor and recipient human cytomegalovirus status on kidney transplantation.

Human cytomegalovirus (HCMV) is considered to be a major pathogen that affects the outcome of solid organ transplantation (TX). Both recipient and donor may be HCMV positive, therefore HCMV re-infection is possible after TX. However, little is known how cytomegalovirus (CMV) transmitted from an infected donor to an infected recipient modulates the recipient's already suppressed immunity, and what the clinical consequences are. To investigate these issues, 52 kidney recipients were followed up for 2 years after TX. T, B and natural killer (NK) lymphocytes, naive and memory T subsets, CD28 expression, relative telomere length, CMV-specific lymphocytes and serum cytokines were measured several times post-TX. Patients were monitored for signs of CMV viremia and other infections. The most important observation was that CMV-specific lymphocytes expand vastly in HCMV-infected recipients who received kidneys from infected donors, in comparison with uninfected donors. Despite this, a higher rate of HCMV viremia was found. Immune deterioration was confirmed by an increased number of CD28-negative T lymphocytes, inverted CD4/CD8 index and shortened telomeres. This was superior in HCMV-infected recipients transplanted from infected donors, when compared with uninfected. In conclusion, CMV alters the immune system in kidney transplant recipients and promotes immune exhaustion.

Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer in the liver and white adipose tissue of rats with experimental chronic renal failure.

Inflammation related to chronic kidney disease (CKD) is an important clinical problem. We recently determined that hepatocyte nuclear factor 1α (HNF1α) was upregulated in the livers of chronic renal failure (CRF) rats-experimental model of CKD. Considering that the promoter region of gene encoding C-reactive protein (CRP) contains binding sites for HNF1α and that the loss-of-function mutation in the Hnfs1α leads to significant reduction in circulating CRP levels, we hypothesized that HNF1α can activate the Crp in CRF rats. Here, we found coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6), HNF1α, and HNF4α in the livers and white adipose tissue (WAT) of CRF rats, as compared to the pair-fed and control animals. This was accompanied by elevated serum levels of CRP and IL-6. CRP and HNFs' mRNA levels correlated positively with CRP and HNFs' protein levels in the liver and WAT. Similar upregulation of the Crp, Il-6, and Hnfs in the liver and WAT and increased serum CRP and IL-6 concentrations were found in lipopolysaccharide (LPS)-induced systemic inflammation in rats. Moreover, silencing HNF1α in HepG2 cells by small interfering RNA led to decrease in CRP mRNA levels. Our results suggests that (a) HNFs act in concert with IL-6 in the upregulation of CRP production by the liver and WAT, leading to an increase in circulating CRP concentration in CRF rats and (b) CRF-related inflammation plays an important role in the upregulation of genes that encode HNFs and CRP in the liver and WAT of CRF rats.

Treatment of Hypertension in Renal Transplant Recipients in Four Independent Cross-Sectional Analyses.

BACKGROUND/AIMS: This retrospective study analysed hypertension management and adherence to blood pressure (BP) targets among renal transplant recipients (RTRs) under specialized care in the Outpatient Transplantation Unit in the Department of Nephrology, Transplantology and Internal Medicine at Gdansk University Hospital. METHODS: Medical records of 101, 316, 639 and 818 RTRs diagnosed with hypertension, who received outpatient care in 2001, 2006, 2011 and 2014, respectively were analysed in four independent cross-sectional surveys. All RTRs received antihypertensive regimens. RESULTS: The overall most commonly used antihypertensive agents were beta-blockers (BB) (range 66.3-82.5%) followed by calcium channel blockers (CCB) (range 52.8-64.2%). Whilst a significant, upward tendency of BB usage (p<0.01) was observed, CCB usage (p<0.001) displayed a downward tendency as a first line therapy in the subsequent years. The average number of antihypertensive agents used per patient increased significantly from 2.24±1.03 in 2001 to 2.55±1.25 in 2014 (p<0.05). The most frequently used combination of hypotensive therapy consisted of two or three antihypertensive drugs depending on the survey. The most common two drug combination consisted of BB and CCB followed by BB accompanied by angiotensin converting enzyme inhibitors. A significant, upward tendency in the use of four (p<0.001) and five (p<0.05) antihypertensive drugs simultaneously, was observed in subsequent years. The target values of BP i.e. <140/90 mmHg were accomplished in 47, 58, 60 and 46% of RTRs in subsequent years. In a secondary - stratified analysis of data from 2014, younger patients (p<0.05), patients with better graft function (p<0.001), patients treated with a higher number of antihypertensive agents (p<0.001) and those not treated with BB (p<0.01) were shown to reach the BP target of below 140/90 mmHg more often. CONCLUSION: The study showed intensification of hypertension treatment in RTRs in subsequent years with BB assuming a dominant role.

[Chronic kidney disease - The relevant information for an occupational physician]. / Przewlekla choroba nerek ­ istotne informacje dla lekarza medycyny pracy.

For a number of years chronic kidney disease (CKD) has been listed in the group of lifestyle diseases, such as obesity, diabetes, cardiovascular disease and hypertension. It is estimated that in Poland more than 4 million people may suffer from various stages of CKD. Chronic kidney disease may also be a consequence of all the other civilization diseases. At the same time it is worth noting that nephrological problems are increasingly being taken into account in modern medical certification. The aim of this work is, among other things, to improve safe access to the labor for patients with kidney diseases. In the legislation existing in our country since 2014 it is stated that chronic renal failure is a potential health contraindication to driving. Also in the annex to the Regulation of the Minister of Health dated 9 December 2015 on health conditions required for seafarers to work on a seagoing ship, it is said that ICD-10 codes (International Classification of Diseases) corresponding to acute and chronic renal failure (N17-N19) should be taken into account when qualifying employees to work at sea. Med Pr 2018;69(1):67-75.

Evaluation of quantitative changes in regulatory T cells in peripheral blood of kidney transplant recipients with skin cancer after conversion to mTOR inhibitors.

INTRODUCTION: Immunosuppressive therapy, necessary for graft survival, has its clinical consequences with an increased risk of developing malignancies being one of them. It seems that the maintenance of a proper balance between cytotoxic and regulatory activity of the immune system may prevent graft rejection, and with a lower risk of cancer. AIM: To assess the quantitative changes in regulatory T cells (Tregs) in peripheral blood of kidney transplant recipients with post-transplantation skin neoplasm after conversion to mTOR inhibitors (mTORi) and to assess the incidence of secondary skin cancer in that group of patients. MATERIAL AND METHODS: Fourteen patients with post-transplant cutaneous malignancies converted to mTORi were included into the study. The control group consisted of eighteen patients maintained on immunosuppressive regimens without mTORi. The level of Tregs with a phenotype defined as CD4lowCD25high was measured before, and 6 months after, mTORi introduction. RESULTS: In all cases, 6 months after conversion, a significant decrease in the ratio of CD4+CD25+ to CD4lowCD25high from 6.52 to 4.29 was detected (p = 0.035). One patient converted to mTORi developed subsequent skin cancer, while in the control group, subsequent skin cancer was recognized in eight patients. Moreover, introducing mTORi significantly improved progression-free survival in this group of patients (p = 0.016). CONCLUSIONS: Introducing mTORi to the immunosuppressive regimen resulted in an increase in the number of regulatory cells without increasing the incidence of secondary skin cancer in the investigated group of patients.

Thiamine Diphosphate Status and Dialysis-Related Losses in End-Stage Kidney Disease Patients Treated with Hemodialysis.

AIM: (1) To describe the whole blood content of thiamine diphosphate (TDP), a biologically active form of vitamin B1 in end-stage kidney disease patients treated with hemodialysis (HD); (2) to establish the impact of a single HD procedure on TDP blood concentrations; and (3) to describe potential explanatory variables influencing TDP dialysis related losses, including dialysis prescription, vitamin B1 dietary intake and supplementation. METHODS: Single-center, cross-sectional study in 50 clinically stable maintenance HD patients. The assessment of whole blood TDP with the High Performance Liquid Chromatography method, before and after a single, middle-week dialysis session and analysis of clinical and laboratory parameters potentially influencing TDP status Results: We report a significant difference in TDP levels before and after HD sessions - 42.5 (95% CI 38.7-46.2) µg/L and 23.6 (95% CI 18.9-28.2) µg/L, respectively (p = 0.000). The magnitude of intradialytic TDP changes is highly variable among individuals and is negatively associated only with the body weight of the patients (p < 0.013). Vitamin B1 dietary intake and supplementation do not influence whole blood TDP and dialysis-related loss of TDP. CONCLUSIONS: TDP, a bioactive compound of vitamin B1, is substantially lost during the HD procedure, and the magnitude of its loss is associated with the patient's body weight but it is not influenced by vitamin B1 dietary intake and standard supplementation dose.

Disorders of serum omega-3 fatty acid composition in dialyzed patients, and their associations with fat mass.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular mortality. Lipid disorders, a constant feature of CKD, might contribute to this state. The aim of this study was to evaluate n-3 polyunsaturated fatty acids (PUFA) composition in CKD patients treated with dialysis, in comparison to the general population and to assess possible associations between the n-3 PUFA profile and anthropometric variables. Thirty-three prevalent dialysis patients were studied and compared with an age- and sex-adjusted control group of 22 patients. Fatty acid composition in serum was analyzed by gas chromatography with a mass spectrometer detector (GC-MS) and anthropometric measures were assessed by bioimpedance spectroscopy. The fatty acid profile of dialyzed patients was characterized by a significantly lower percentage content of n-3 PUFA. For α-linolenic acid (ALA), it was 0.21 ± 0.09% in dialysis patients versus 0.33 ± 0.11% in the control group (p < .001). For eicosapentanoic acid (EPA), 0.59 ± 0.23% versus 1.15 ± 0.87% (p < .001), and for docosahexaenoic acid (DHA) 1.11 ± 0.50% versus 1.75 ± 0.87% (p < .001), respectively. The amount of n-3 PUFA decreased with time on dialysis and it correlated positively with body fat mass. For DHA, this correlation was r = .48 (p < .01) and for EPA r = .40 (p < .05). Patients with CKD have a relatively low content of n-3 PUFA which may contribute to their high cardiovascular risk. Patients with a higher content of body fat are characterized by a favorable fatty acid composition.

[Health awareness and cooperation with the patient in the therapeutic process in a population of patients with chronic kidney disease in the center of Gdansk].

Chronic kidney disease (CKD) is considered as a disease of civilization of the XXI century. The increase of patients with CKD is associated with a higher incidence of hypertension, diabetes and aging. Hypertension occurs in 60-90% of patients with CKD. It is worth to underline that the nephroprotective therapy can delay or even stop the progression of CKD to end-stage renal disease. The therapy nephroprotective should be understood as both pharmacological and nonpharmacological treatment. The aim of this study was to evaluate the health awareness of patients with CKD, as well as the degree of patient compliance especially in terms of pharmacological and non-pharmacological treatment. Material and Methods: A crosssectional survey was offered for 1300 patients with CKD who are are under the care of the Department of Nephrology, Transplantology and Internal Medicine, University Hospital in Gdansk. 972 patients (M/F) (74.8%) responded positively to participate in the study Results: It was shown that 91.2% of the patients measured blood pressure at home. 41.2% measured blood pressure everyday and 54.2% of patients used at least one non-pharmacological treatment for hypertension. 71.7% of patients declared that buy all drugs prescribed by the doctor. 53.4% of patients used the possibility of substitution drugs prescribed by a doctor for cheaper preparations recommended by the pharmacist. 85.7% of patients taking medicines according to doctor's advice (frequency, dose). Conclusions: The results of the study indicate that the education of patients, the therapeutic process and their health awareness are good, especially among patients treated with peritoneal dialysis. It should be continued as educational program because these activities may contribute to improving the prognosis and quality of life. A patients after kidney transplantation are particularly vulnerable to the effects of failure to comply with recommendations.

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease. MATERIAL AND METHODS: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009. RESULTS: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%). CONCLUSIONS: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.

Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial.

BACKGROUND: Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/Vurea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control. STUDY DESIGN: Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/Vurea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of -0.5. SETTING & PARTICIPANTS: Hypertensive patients (≥ 1 antihypertensive drug, including diuretics, or office systolic BP ≥ 130 mmHg) on continuous ambulatory PD therapy from 17 sites. INTERVENTION: 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution. OUTCOMES: Primary end point: weekly total Kt/Vurea; secondary outcomes: BP control, safety, and tolerability. MEASUREMENTS: Total Kt/Vurea was determined from 24-hour dialysate and urine collection; BP, by office measurement. RESULTS: Total Kt/Vurea after 12 weeks was 2.53 ± 0.89 in the low-sodium group (n = 40) and 2.97 ± 1.58 in the control group (n = 42). The noninferiority of total Kt/Vurea could not be confirmed. There was no difference for peritoneal Kt/Vurea (1.70 ± 0.38 with low sodium, 1.77 ± 0.44 with standard sodium), but there was a difference in renal Kt/Vurea (0.83 ± 0.80 with low sodium, 1.20 ± 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P < 0.001). BP changed marginally with standard-sodium solution, but decreased with low-sodium PD solution, resulting in less antihypertensive medication. LIMITATIONS: Broader variability of study population than anticipated, particularly regarding residual kidney function. CONCLUSIONS: The noninferiority of the low-sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP.

Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure.

Dyslipidemia commonly present in patients with chronic kidney disease (CKD) has been recently linked to increased proprotein convertase subtilisin/kexin type 9 (PCSK9) serum concentration. We tested a hypothesis that increased liver PCSK9 biosynthesis could be partially responsible for the elevated circulating PCSK9 level, and subsequently contribute to hypercholesterolemia observed in subjects with CKD. Rat model of chronic renal failure (CRF) was used in the study. Animals underwent a 5/6 nephrectomy or a sham operation. Liver expression of Pcsk9, sterol regulatory element-binding transcription factor 2 (Srebf-2), and ß-actin were quantified by real-time RT-PCR. Liver protein levels of PCSK9, LDL-receptor (LDL-R), and SREBF-2 were analyzed using Western blotting. Serum PCSK9 concentration was estimated by immunoassay. Rats with an experimental CRF as compared to pair-fed and control ones were characterized by: (a) an up-regulation of liver Pcsk9 and Srebf-2 genes expression with parallel increase of serum PCSK9 concentration; (b) a decrease in liver LDL-R protein level, and (c) an increase of serum total and LDL-cholesterol concentrations. We also found significant correlations between serum creatinine and liver PCSK9 mRNA levels (r = 0.88, p < 0.001) and between serum creatinine and circulating PCSK9 levels (r = 0.73, p < 0.001). The results suggest that a rat model of CRF is associated with an increased liver Pcsk9 gene expression. The coordinated up-regulation of Pcsk9 and Srebf-2 genes expression suggests that SREBF-2 may play a key role in regulation of Pcsk9 gene expression, circulating PCSK9 level, and hypercholesterolemia in experimental CRF.

Prevalence of chronic kidney disease in a representative sample of the Polish population: results of the NATPOL 2011 survey.

BACKGROUND: Chronic kidney disease (CKD) has been proven to be a major risk factor of cardiovascular disease (CVD). Until now, data on the prevalence of CKD among adults in Poland were limited. The NATPOL 2011 survey is a cross-sectional observational study designed to assess the prevalence and control of CVD risk factors in Poland, and the first study capable of evaluating CKD prevalence in adult Polish citizens. METHODS: Serum creatinine concentration and the urine albumin-to-creatinine ratio (ACR) were measured in 2413 randomly selected participants (ages 18-79 years) from a national survey study. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m(2) or ≥60 mL/min/1.73 m(2) with coexisting albuminuria (ACR ≥ 30 mg/g). Additionally, comorbidities and anthropometric and social factors related to the prevalence of CKD were analysed. RESULTS: The prevalence of CKD was estimated at 5.8% [95% confidence interval (95% CI) 4.6-7.2] using Chronic Kidney Disease Epidemiology Collaboration formula. The general prevalence was higher when the MDRD was applied [6.2% (95% CI 4.0-7.6)]. An eGFR <60 mL/min/1.73 m(2) was found in 1.9% (95% CI 1.5-2.5) of the studied population. This was accompanied by low awareness of this condition (14.9%). The frequency of albuminuria was estimated at 4.5% (95% CI 3.4-5.9). Diabetes mellitus (DM) and arterial hypertension (AH) were more frequent among respondents with diagnosed CKD compared with those without CKD [18.5 versus 4.5% (P < 0.001) and 67.8 versus 29.0% (P < 0.001) respectively]. DM and AH were, apart from increasing age, the two greatest risk factors of CKD. CONCLUSION: The estimated prevalence of CKD among adults in Poland is 5.8% (∼1 724 960 patients). Its prevalence was lower than expected. CKD is more frequent in older subjects, smokers and people with comorbidities such as AH and DM.

Disorders of the anterior attentional-intentional system in patients with end stage renal disease: Evidence from reaction time studies.

OBJECTIVE: Dialyzed patients with end-stage renal disease (ESRD) have been reported to have several neurobehavioral impairments that are often accompanied by structural and functional abnormalities of frontal-subcortical networks. Whereas the anterior attentional-intentional systems responsible for the allocation of attention and preparation for action (intention) are mediated by these frontal-subcortical networks, these functions have not been specifically investigated in this population. METHOD: Twenty-three non-demented dialyzed patients with ESRD were compared with 25 matched controls on the performance on four reaction time (RT) subtests from the ROtman-Baycrest Battery to Investigate Attention (ROBBIA). These included measures of Simple, Choice, and Prepare RTs as well as a Concentrate task. RESULTS: In the Prepare RT task with a warning signal presented 1s before the onset of imperative stimulus, the patients' performance was not different than the controls; however, dialyzed patients became significantly slower than controls in the Prepare 3s warning condition as well as on all other RT measures. Nonetheless, both groups exhibited a gradual decrease in RT with increasing interstimulus intervals, with no group difference in the number and type of errors. CONCLUSIONS: These results suggests, that while with external preparatory stimuli, the dialyzed ESRD patients may be able to acutely increase their arousal and enhance their allocation of selective attention or action-preparation, they appear not to be able to maintain this enhanced preparatory status. Whereas these results help to elucidate a potential source of disability in this patient population, future studies will need to examine if this deficit is primarily attentional, intentional or both (arousal), as well as explore possible treatments.

Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study.

BACKGROUND: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. METHODS: COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. RESULTS: Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and <168 pg/mL (PTH), respectively, were associated with improved survival. CONCLUSIONS: COSMOS provides evidence of the association of serum phosphorus, calcium and PTH and mortality, and suggests survival benefits of controlling chronic kidney disease-mineral and bone disorder biochemical parameters in CKD5D patients.

Treatment of hypertension in chronic kidney disease patients under specialized care: one-center cross-sectional analyses.

AIM: The study analyzed hypertension management and control rates among non-dialysis, non-transplanted hypertensive chronic kidney disease (CKD) patients under specialized care in Gdansk nephrology center in 1996-2011. PATIENTS AND METHODS: It was a retrospective, cross-sectional study analyzing data from medical records of 190, 490, 1799 and 1696 subjects with CKD, who received outpatient care in 1996, 2001, 2006 and 2011, and were included in four independent surveys, respectively. RESULTS: The average number of antihypertensive drugs per patient increased significantly (p < 0.01) as follows 1.74 ± 0.9 (1996), 2.08 ± 1.01 (2011), 2.5 ± 1.19 (2006) and 2.65 ± 1.18 (2011). The percentage of patients receiving diuretics, beta-blockers and drugs inhibiting renin-angiotensin-aldosterone increased significantly in subsequent years, while a frequency of therapy with calcium channel blockers decreased (p < 0.001). 16%, 30%, 42% and 54% of subjects had causal BP values < 140/90 mmHg (p < 0.001). When specific thresholds for CKD patients according to JNC recommendations were used, the control rate was worse but also showed significant improvement in the second, third and final surveys, i.e. 9%, 12%, 14% and 24% (p < 0.001). The subgroup analysis revealed that a better control rate was observed in following groups: < 65 years old; I-II stage of CKD; primary glomerulonephritis; without cardiovascular complications or diabetes. CONCLUSION: The study may show an improvement in the effectiveness of antihypertensive treatment in CKD patients under specialized care in Gdansk Nephrology Centre in 1996-2011.

Nephroprotective action of renin-angiotensin-aldosterone system blockade in chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D trails.

The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently the most effective strategy that combines blood pressure lowering and renoprotection. Several large, randomized, controlled trials evidenced the renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in nephropathies of almost any etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor, aliskiren, as add-on treatments to standard therapy including the optimal dose of ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal dysfunction more than placebo. No clinical evidence is available however about whether these strategies may influence on long-term kidney outcome. Three recent trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS-blocking agents, does not decrease cardiovascular and renal morbidity and may carry an increased risk of serious complications. This article reviews an evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney disease and considers the implementation of dual RAAS blockade with reference to the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their treatment decisions for patients with chronic kidney disease.