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Abstract: Anemia is more prevalent in allograft recipients compared with glomerular filtration rate (GFR) matched patients with chronic kidney diseases. There is a paucity of data concerning the correction of anemia in the posttransplant period with erythropoietin-stimulating agents (ESA). The aim of this study was to compare the iron status, kidney function, inflammatory state, use of drugs affecting erythropoiesis (immunosuppressants ACEi/ARB) and correction of anemia using ESA in a chronic kidney disease (CKD) population versus kidney transplant recipients. We included 67 patients treated with ESA including 17 after kidney transplantation. CKD Patients with native kidneys were significantly older than allograft recipients (mean age 69 versus 51 years; P < .001, and despite similar serum creatinine and iron parameters showed an estimated lower GFR (19 mL/min versus 23 mL/min; P < .05). Median time of ESA therapy was similar among patients with native kidney CKD versus kidney recipients, but they achieved a significantly higher hemoglobin (11.04 versus 10.36 g/dL; P < .05). There was no difference between patients administered or not a mammalian target of rapamycin antagonist. None of the patients with native kidney CKD received immunosuppressive therapy, but they were prescribed ACEi more often than kidney recipients. The higher degree of anemia in kidney allograft recipient is the most probably attributed to the use of immunosuppressive drugs, despite their better kidney function and comparable iron status. This study suggested that higher doses of ESA should be employed to anemia in kidney transplant recipients. [Copyright &y& Elsevier]

Abstract: Hepcidin is a small, defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. We studied correlations of hepcidin concentrations with markers of iron status, erythropoietin therapy, and markers of inflammation among 130 kidney allograft recipients. In addition, we assessed the prevalence of anemia and its relation to hepcidin. Soluble receptor of transferrin (sTfR), high-sensitivity C-reactive protein (hsCRP), TNF-α, interleukin (IL)-6, prohepcidin, and hepcidin were measured using commercially available kits. According to the WHO definition, the prevalence of anemia was 28%. Among anemic recipients we found a significantly higher values of serum creatinine, serum prohepcidin, hepcidin, (hsCRP), TNF-α, IL-6, ferritin, and proteinuria in addition to more frequent use of rapamycin and significantly lower use of CSA with lower CSA concentrations, as well as lower cholesterol, hemoglobin, and estimated glomerular filtration rate (eGFR) (by the Modification of Diet in Renal Disease equation). Serum prohepcidin significantly correlated with creatinine, GFR, time after transplantation, albumin, hsCRP, IL-6, and TNF-α, whereas hepcidin-25 correlated with serum iron, ferritin, hsCRP, IL-6, hemoglobin, transferrin saturation (TSAT), creatinine, and GFR. Multiple regression analysis showed that prohepcidin was independently related only to GFR and ferritin. Upon multiple regression analysis, predictors of serum hepcidin were eGFR, ferritin, and hsCRP, explaining 79% of the variation of hepcidin values. In conclusion, the prevalence of anemia was relatively high among a population of kidney allograft recipients. The pathogenesis of anemia is mulitfactorial. Elevated hepcidin levels among kidney transplant recipients may be due to low-grade inflammation, which is frequently encountered in this population, and mainly to impaired renal function, but it did not seem to be a major pathogenetic factor for anemia in this population. [Copyright &y& Elsevier]

Abstract: Visfatin, a ubiquitous adipokine, was first described in 2005. It was found to be selectively up-regulated in the adipose tissue and to have insulin-mimetic effects. It has been reported that visfatin is associated with endothelial damage in chronic kidney disease. We investigated plasma visfatin levels (using commercially available kits) in 100 clinically stable kidney allograft recipients. We assessed visfatin markers of coagulation: thrombin-antithrombin complexes, prothrombin fragments 1 + 2; fibrinolysis: tissue plasminogen activator, plasminogen activator inhibitor, plasmin-antiplasmin complexes; endothelial function/injury: von Willebrand factor, thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule (VCAM); inflammation: hsCRP and interleukin-6. Visfatin was significantly higher in kidney allograft recipients than in healthy volunteers. Visfatin did not differ significantly between diabetic and nondiabetics, hypertensives and normotensives, patients with and without coronary artery disease, and between male and female subjects. Type of immunosuppressive regimen (mycophenolate mofetil vs azathioprine) did not affect visfatin levels. On univariate analysis, visfatin correlated positively with prothrombin fragments 1 + 2, VCAM, creatinine, high-sensitivity C-reactive protein, and negatively with albumin. In multivariate analysis, only VCAM was associated with visfatin in kidney allograft recipients. Visfatin, which is related to markers of inflammation, may represent a novel link between inflammation and adipocytokines among long-term kidney transplant recipients. [Copyright &y& Elsevier]

Aims: To assess the number of people with diabetes in Poland using combined national sources and to evaluate the usefulness of data from an insurance system for epidemiological purposes. Methods: The data were collected from four sources: 1) 2013 all‐billing records of the national insurance system comprising people of all age groups undergoing procedures or receiving services in primary healthcare, specialist practices and hospitals and also those receiving drugs; 2) an epidemiological study, NATPOL, that involved the assessment of people with undiagnosed diabetes; 3) the RECEPTOmetr Sequence study on prescriptions; and 4) regional child diabetes registries. Results: In 2013, 1.76 million people (0.98 million women and 0.79 million men) had medical consultations (coded E10‐E14) and 2.13 million people (1.19 million women and 0.94 million men) purchased drugs or strip tests for diabetes. A total of 0.04 million people who used medical services did not buy drugs. In total, the number of people with diabetes in the insurance system was 2.16 million (1.21 million women and 0.95 million men), which corresponds to 6.1% (95% CI 6.11–6.14) of women and 5.1% (95% CI 5.12–5.14) of men. Including undiagnosed cases, the total number of people with diabetes in Poland was 2.68 million in 2013. Conclusion: The estimated prevalence of diabetes (diagnosed and undiagnosed cases) in Poland is 6.97%. Data from the national insurance system with full coverage of the population can be treated as a reliable source of information on diseases with well‐defined diagnosis and treatment methods, combined with an assessment of the number of undiagnosed individuals. What's new?: The present study is a unique attempt to assess diabetes prevalence in one of the biggest countries in Central and Eastern Europe.The prevalence of diabetes estimates presented to date rely on studies covering selected populations in different regions of Poland.The present analysis was conducted on the basis of a complete database of contracted medical services and reimbursed drugs from the only public insurance in the country and from population studies (NATPOL and POLSENIOR), and led to a diabetes prevalence estimate of 6.97%.The study shows the high burden of diabetes and the need for a complete diabetes register for monitoring health needs and diabetes control. [ABSTRACT FROM AUTHOR]

Aims To present the incidence trend for Type 1 diabetes in Polish children aged 0-14 years, updated using data collected during 2005-2012, and assess the reliability of the predictive model constructed previously using the 1989-2004 database. Methods Children aged < 15 years with newly diagnosed Type 1 diabetes are recorded prospectively ( EURODIAB criteria) in several regional registers in Poland. Age- and gender-standardized incidence rates for Type 1 diabetes were calculated per 100 000 persons/year. Incidence rates were analysed in terms of the dependency on age, gender, geographical region and population density. Incidence rate trends over time were modelled using generalized linear models. Results The mean standardized incidence for 1989-2012 was 12.72 per 100 000 persons/year [95% confidence interval ( CI), 11.35 to 14.21]. Over the 24-year observation period, the incidence increased from 5.36 to 22.74 per 100 000 persons/year. The lowest incidence rate was in children aged 0-4 years (8.35, 95% CI 7.27 to 9.57 per 100 000 persons/year). There was no difference between genders, or urban and rural regions. Incidence rates were higher in northern compared with southern Poland [14.04 (95% CI 12.59 to 15.63) vs. 11.94 (95% CI 10.62 to 13.39) per 100 000 persons/year]. The new data corrected the earlier predictive model by changing the estimates of some factors related to patient age, gender and their interactions with the remaining factors. The incidence rate shows periodic 5.33-year fluctuations. The periodicity component allows for a more accurate prediction of the incidence rate over time. Conclusions This cohort study reveals a sustained increase in Type 1 diabetes incidence in Polish children aged 0-14 years with regular, sinusoidal fluctuations and a slight levelling off in past few years. It is of concern that are the highest increases in incidence are found in children aged 0-4 years. [ABSTRACT FROM AUTHOR]

Deterioration of glomerular filtration rate (GFR) is associated with alterations of bone metabolism. It translates clinically to bone fragility and increased fractures rate among patients with impaired GFR. Recently, sclerostin (SCL) gained much attention as an important factor in pathogenesis of mineral and bone disturbances in patients with renal diseases. There is no data about SCL behaviour in patients with acute GFR decline. The aim of this study was to evaluate the renal handling of SCL. This is a prospective, single-centre observational study in patients undergoing nephrectomy due to urological indications. Serum and urinary SCL levels were measured prior and after nephrectomy. 25 patients were enrolled. After surgery, eGFR significantly declined (from 87.4 ± 19.7 to 67.7 ± 25.7 ml/min/1.73 m², p < 0.0001). Nephrectomy caused more than 20 times higher renal fractional excretion of SCL [0.15 (interquartile range, IQR 0.09-0.40) vs. 2.78 (IQR 1.51-4.02) %, p < 0.001], while its serum level remained intact [0.69 (IQR 0.57-0.90 vs. 0.65 (IQR 0.53-0.88) ng/ml, p = 0.4]. The magnitude of eGFR reduction was associated inversely with change in urinary SCL fractional excretion (r = -0.6, p = 0.001) and with alteration in serum SCL level (r = -0.5, p = 0.01). Our results suggest that increased serum SCL concentrations at moderately reduced GFR are not due to diminished renal clearance. At more severely decreased GFR, elevated SCL concentration results from both increased production and reduced renal elimination. [ABSTRACT FROM AUTHOR]

Background Kaposi sarcoma (KS) is a cancer with an incidence in patients after transplantation (Tx) that is 500 times greater than that in the healthy population. The risk of KS increases significantly during therapy, especially when immunosuppressive therapy with cyclosporine A (CsA) is used. Most cases of KS develop during the first 2 years after transplantation. After a KS diagnosis, it is recommended to reduce the doses of immunosuppressive medications. Conversion of immunosuppressive treatment into mammalian target of rapamycin (m-TOR) inhibitors is strongly suggested. Patients and Methods We present the case of a 65-year-old man with end-stage renal disease (ESRD) of unknown etiology, who had kidney transplantation in 2008. Immunosuppressive protocol was based on CsA, mycophenolate mofetil (MMF) and prednisolone (PRE). In 2011, during the dermatological consultation, on the penis glans a purple stain of uneven surface was noted. Histology study revealed the presence of KS. The treatment was modified. The patient was converted from CsA to everolimus. Before converting, the creatinine concentration was 1.79 mg/dl and proteinuria less than 0.3 g/day. Results The change in the scheme of immunosuppresion from CsA to everolimus was performed to treat the Kaposi sarcoma. Gradually, within a year, the KS was cured. However, the graft function deteriorated, and the graft was lost in one-years’ time. Conclusion We present the first documented case of KS in the genital area of a kidney patient. The reduction in the strength of immunosuppression, and the introduction of an m-TOR inhibitor, may have contributed to the deterioration of kidney function, however it was substantial in the treatment of KS. [ABSTRACT FROM AUTHOR]

Aims: Wolfram syndrome (WFS) is diagnosed as coexistence of diabetes mellitus and optic atrophy, where pancreatic beta cell destruction is associated with neurodegeneration. Typically, WFS necessitates insulin treatment similar to type 1 diabetes (T1D), but the mechanism of beta cell mass reduction leading to hyperglycemia is different. Methods: The aim of the study was to assess glycemic variability using the continuous glucose monitoring (CGM) system in seven pediatric patients with genetically confirmed WFS and compare the results with data obtained from 21 propensity score-matched patients with T1D. The 'GlyCulator' application was used for the calculation of glycemic variability indices. Results: CGM recordings showed similarities in glycemic variability among WFS patients, but differing from those of the T1D group. Coefficient of variation (%CV), CONGA4h, and GONGA6h were significantly ( p < 0.05) lower in WFS patients (28.08 ± 7.37, 54.96 ± 11.92, and 55.99 ± 10.58) than in T1D patients (37.87 ± 14.24, 74.12 ± 28.74, p = 0.02, and 80.26 ± 35.05, respectively). In WFS patients, the percentage of values above 126 mg/dL was 69.79 (52.08-77.43), whereas in patients with T1D, the percentage was significantly lower-47.22 (35.07-62.85, p = 0.018). Curiously, a tendency toward a lower percentage of measurements below 70 mg/dL was noted in the WFS group [0 (0-7.29)] in comparison with the T1D group [6.25 (0-18.06), p = 0.122]. WFS patients had a significantly higher C-peptide level (0.31 ± 0.2 ng/mL) than T1D patients (0.04 ± 0.04 ng/mL; p = 0.006). Conclusions: Patients with WFS show smaller glycemic variability than individuals with T1D, and this may be associated with persistent residual insulin secretion. [ABSTRACT FROM AUTHOR]

Minitablets are a novel, multi-compartment solid drug formulation, particularly intended for children between 1 and 6 years of age. Available literature shows that even infants are capable of swallowing a single minitablet. In this study, we have explored the level of acceptance of minitablets administered in units of 5 or 10. A group of thirty two 2-year-old children (2-years) and twenty eight 3-year-old children (3-years) have been enrolled in the study. Each child was asked to swallow placebo minitablets (2 mm or 3 mm) suspended in a fruity jelly on a spoon. The swallowing of minitablets (with or without chewing) was registered for 75% of 2-year-olds and for 93% of 3-year-olds. Moreover, most of the children (57% of all participants) were fully capable of swallowing all units without chewing (2-years: 50%; 3-years: 64%). However, no statistically significant differences in the swallowing ability were observed in gender and age groups. None of the children choked. Neither the number, nor the diameter of the administered minitablets have significantly influenced the ability to swallow units. The results show that minitablets administered in several units mixed with jelly food are safe and could be accepted by a pediatric population. [ABSTRACT FROM AUTHOR]

Abstract: Background: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semicarbazide-sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus, and obesity. The aim of the study was to assess VAP-1 in prevalent heart and kidney allograft recipients. Methods: Complete blood count, urea, serum lipids, fasting glucose, and creatinine were studied by standard laboratory methods. VAP-1, N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were estimated using commercially available assays. Results: Healthy volunteers showed higher hemoglobin and estimated glomerular filtration rate (eGFR) but lower creatinine, NT-proBNP, hsCRP and VAP-1 relative to heart and kidney transplantation (OHT) (KTx). Among heart transplant recipients, VAP-1 correlated with age, presence of diabetes, insulin therapy, ejection fraction, estimated glomerular filtration rate by MDRD (Modification of Diet in Renal Disease), eGFR by CKD-EPI (Chronic Kidney Disease-Epidemiological Collaboration), use of tacrolimus, LVIDd (left ventricular internal end-diastolic dimension), New York Heart Association class and NT-proBNP. VAP-1 was significantly lower among patients treated with tacrolimus than cyclosporine. Diabetic patients versus nondiabetic subjects as well as patients with eGFR below 60 versus ≥ 60 mL/min showed higher serum VAP-1 in OHT and KTx populations. Multiple regression analysis revealed VAP-1 to be predicted in 25% by LVIDd, and use of tacrolimus in OHT. In kidney transplant recipients, VAP-1 correlated only with time after transplantation and serum glucose. Concluding: VAP-1 elevations in heart transplant recipients were predominantly dependent on left ventricular diameter and use of tacrolimus; however, the precise associations with the immunosuppressive regimen warrant further studies. VAP-1 elevations in kidney transplant recipients may relate to glucose control. [Copyright &y& Elsevier]