Subthreshold rejection activity in many kidney transplants currently classified as having no rejection.

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

[Water-sodium homeostasis in hemodialysis - the eternal problem in nephrology practice]. / Homeostaza wodno-sodowa w hemodializie ­ odwieczny problem w praktyce nefrologicznej.

The kidney is an organ that maintains the body's sodium and water balance and plays a significant role in blood pressure regulation. Chronic kidney disease (CKD) and a progressive loss of its function, among others, leads to sodium and water retention and, as a consequence, to arterial hypertension. The supply of salt and fluids delivered with the diet significantly affects the cardiovascular system's functioning particularly in hemodialysis patients. The critical element in clinical care is maintaining appropriate water and electrolyte homeostasis. Overhydration is manifested as oedema and blood preassure increase, but a more accurate assessment of subtle variations is possible by measuring bioelectric impedance (BIA), which determines the extracellular water index (ECW). Actions to maintain euvolemia include limiting sodium and fluid intake, regular assessment of "dry" body weight, proper selection of ultrafiltration (UF), correction of sodium concentration, and dialysate temperature.

[Systemic sclerosis. Part 2. Epigenetic factors in the pathogenesis of clinical manifestations]. / Twardzina ukladowa. Czesc 2. Czynniki epigenetyczne w patogenezie objawów klinicznych.

Systemic sclerosis is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and vasculopathy affecting predominantly the microvessels with a predilection for women. The genetic background of systemic sclerosis is still full of unanswered questions, with classical genetics able to explain only some systemic sclerosis cases. Novel advances concerning epigenetics give us new insight into pathogenesis of systemic sclerosis. This review focuses on results of recent reports on epigenetic modifications of the gene functions and X inactivation changes in pathogenesis of systemic sclerosis. Current evidence demonstrates DNA heavy methylation (FLI1, NOS3, BMPRII) and hypomethylation of regulatory genes (CD40L, CD70), histone code modifications, abnormal expression of large spectrum of microRNAs.

APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.

Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.

[Systemic sclerosis. Part 1: searching for genetic determinants]. / Twardzina ukladowa. Czesc 1: poszukiwanie genetycznych uwarunkowan.

Familial aggregation of systemic sclerosis observed in the 1970 of twenty century, the presence of karyotype instability and chromosomal mosaicism and positive associations of certain polymorphisms of genes located in specific regions of the human genome may indicate the important contribution of genetic factors in the development and progression of the disease. The purpose of this paper is to present data on genetic changes found in scleroderma. Despite the enormous progress of research it is not yet clear, which disturbances in a specific way determine onset and development of the disease and which are non-specific forms of molecular abnormalities also present in other diseases with similar clinical symptoms.

Thrombolome and Its Emerging Role in Chronic Kidney Diseases.

Patients with chronic kidney disease (CKD) are at an increased risk of thromboembolic complications, including myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. These complications lead to increased mortality. Evidence points to the key role of CKD-associated dysbiosis and its effect via the generation of gut microbial metabolites in inducing the prothrombotic phenotype. This phenomenon is known as thrombolome, a panel of intestinal bacteria-derived uremic toxins that enhance thrombosis via increased tissue factor expression, platelet hyperactivity, microparticles release, and endothelial dysfunction. This review discusses the role of uremic toxins derived from gut-microbiota metabolism of dietary tryptophan (indoxyl sulfate (IS), indole-3-acetic acid (IAA), kynurenine (KYN)), phenylalanine/tyrosine (p-cresol sulfate (PCS), p-cresol glucuronide (PCG), phenylacetylglutamine (PAGln)) and choline/phosphatidylcholine (trimethylamine N-oxide (TMAO)) in spontaneously induced thrombosis. The increase in the generation of gut microbial uremic toxins, the activation of aryl hydrocarbon (AhRs) and platelet adrenergic (ARs) receptors, and the nuclear factor kappa B (NF-κB) signaling pathway can serve as potential targets during the prevention of thromboembolic events. They can also help create a new therapeutic approach in the CKD population.

Health Care Resources and 24,910 Deaths Due to Traffic Accidents: An Ecological Mortality Study in Poland.

BACKGROUND: Deaths due to traffic accidents are preventable and the access to health care is an important determinant of traffic accident case fatality. This study aimed to assess the relation between mortality due to traffic accidents and health care resources (HCR), at the population level, in 66 sub-regions of Poland. METHODS: An area-based HCR index was delivered from the rates of physicians, nurses, and hospital beds. Associations between mortality from traffic accidents and the HCR index were tested using multivariate Poisson regression models. RESULTS: In the sub-regions studied, the average mortality from traffic accidents was 11.7 in 2010 and 9.3/100.000 in 2015. After adjusting for sex, age and over time trends in mortality, out-of-hospital deaths were more frequently compared to hospitalized fatal cases (incidence rate ratio (IRR) = 1.68, 95% CI 1.45-1.93). Compared to sub-regions with high HCR, mortality from traffic accidents was higher in sub-regions with low and moderate HCR (IRR = 1.25, 95% CI 1.11-1.42 and IRR = 1.19, 95% CI 1.02-1.38, respectively), which reflected the differences in out-of-hospital mortality most pronounced in car accidents. CONCLUSIONS: Poor HCR is an important factor that explains the territorial differentiation of mortality due to traffic accidents in Poland. The high percentage of out-of-hospital deaths indicates the importance of preventive measures and the need for improvement in access to health care to reduce mortality due to traffic accidents.

Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1 adenosine receptors.

Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle alpha-actin promoter and first intron (12). Two founder lines with highest expression in the kidney [353 +/- 42 and 575 +/- 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N6-cyclohexyladenosine. Maximum TGF responses (0-30 nl/min flow step) were increased from 8.4 +/- 0.9 mmHg in WT (n = 21) to 14.2 +/- 0.7 mmHg in A1AR-transgene (tg) 4 (n = 22; P < 0.0001), and to 12.6 +/- 1.2 mmHg in A1AR-tg7 (n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5-10 and 10-15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 +/- 1.5 nl/min compared with 2.6 +/- 0.51 nl/min in WT (P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses.

Is socio-economic status associated with adverse birth outcomes in Poland?

INTRODUCTION: Low birth weight (LBW) is an important indicator of the healthy of the population and reflects the living conditions, health and health behaviours of pregnant women. OBJECTIVE: To assess the relationship between Gross Enrollment Rate at the Tertiary Education Level, average salary, Gross Domestic Product per capita, unemployment, housing area, urbanization and low birth weight in Polish sub-regions. MATERIAL AND METHODS: An ecological study was undertaken using data on socio-economic and demographic features and LBW in 2005-2014. The units of observation were 66 Polish sub-regions according to the NUTS-3 classification. Two models were used to assess the influence of SES variables on LBW incidence rate in a 10-year study period. The first was the Poisson regression model adjusted for density of population, which was followed by the multivariable model using the GEE method of model parameters estimation. RESULTS: In Poland, significant slow changes in the LBW incidence rate were observed in 2005-2014 (AAPC = -0.44%/year). In model 1, the increase in LBW was associated with an increase in unemployment (1.005) and decrease of average salary (0.987), GERTEL (0.990) and housing area (0.991). In model 2, an unfavorable association was detected between the density of population (1.068) and a still existing relationship with unemployment (1.004), average salary (0.990) and GERTEL (0.991). CONCLUSIONS: Protective factors for newborns' health were a higher level of education and income. The results indicate the need to take actions to reduce the risk factors of LBW among pregnant women living in densely populated areas.

Area-Based Socio-Economic Inequalities in Mortality from Lung Cancer and Respiratory Diseases.

Background: After political transformation in 1989/1990, Poland experienced a general improvement in living conditions and quality of life, but the benefits did not extend evenly across all segments of the society. We hypothesized that the regional differences in mortality due to diseases of the respiratory system are related to socioeconomic status (SES) and its changes over time. Materials and methods: An ecological study was carried out in 66 sub-regions of Poland using the data from the period of 2010 to 2014. Age-standardized mortality rates (SMRs) were calculated separately for men and women in three age categories: ≥15, 25-64 years, and ≥65 years. An area-based SES index was derived from the characteristics of the sub-regions using the z-score method. Multiple weighted linear regression models were constructed to estimate a real socioeconomic gradient for mortality resulting from lung cancer and respiratory diseases. Results: In the regions studied, the SMRs for respiratory disease varied from 70/100,000 to 215/100,000 in men and from 18/100,000 to 53/100,000 in women. The SMRs for lung cancer varied from 36/100,000 to 110/100,000 among men and from 26/100,000 to 77/100,000 among women. After adjusting for the prevalence of smoking and environmental pollution, the SES index was found to be inversely associated with the SMR for lung cancer in each category of age among men, and in the age group of 25-64 years among women. An increase of the SES index between 2010 and 2014 was associated with a decrease of SMR for respiratory disease both in men and women, but this change was not significantly associated with the SMR for lung cancer. Conclusion: SES appears to be an important correlate of mortality from respiratory diseases and lung cancer at the population level, particularly in men. A lower SES was associated with greater mortality from lung cancer and respiratory diseases. An increase in SES over time was related to a decrease in mortality from respiratory disease, but not from lung cancer.

Oral health-related quality of life in patients undergoing chronic hemodialysis.

AIMS: The aims of the study were to determine oral health-related quality of life (OHRQoL) in chronic hemodialysis (HD) patients and to estimate which scale describing OHRQoL, Oral Health Impact Profile (OHIP-14) or Geriatric/General Oral Health Assessment Index (GOHAI), was more useful in this particular group. METHODS: This was a cross-sectional study conducted by means of a census survey. The Polish versions of OHIP-14 and GOHAI were used to assess OHRQoL. The oral examination included decayed, missing and filled teeth (DMF-T) Index; Oral Hygiene Index simplified; Plaque Index and Gingival Index. In the statistical analysis, the Kruskal-Wallis test, Mann-Whitney U test, Pearson's χ2 test and Spearman's rank correlation coefficients were used as appropriate. RESULTS: The final sample consisted of 72 patients (mean age 63.2±15.2 years). The mean duration of HD treatment was 43.8 months. The mean number of teeth was 10.9. The majority of participants (81.9%) were dentate; only 22.2% of the respondents had >20 teeth. Among the dentate subjects, 44.1% wore removable dental prostheses (60.7% women). The most prevalent items for GOHAI (mean 14.71; SD 7.21) were uncomfortable to swallow, discomfort when eating and unhappy with appearance. The most prevalent items for OHIP-14 (mean 8.87; SD 10.95) were uncomfortable to eat foods, and diet has been unsatisfactory. The internal reliability (Cronbach's alpha) was 0.637 for GOHAI and 0.918 for OHIP-14. Chewing problems were significantly related to GOHAI (p=0.001) and OHIP-14 (p<0.001) scales. Higher OHIP-14 scores were significantly associated with dental treatment needs (p=0.029) and poor self-rated oral status (p=0.001). CONCLUSION: The HD patients had an unsatisfactory oral status, but using only OHRQoL scale was insufficient to capture all their oral health problems. The scales did not fully reflect poor oral health in HD patients. The oral problems were not a major concern for this group of patients, which could indicate the adaptation to impaired oral health or a change in health priorities. Regular dental examinations together with the assessment of OHRQoL in HD patients are required for a comprehensive patients' state. In our study, more variables were significantly related to the OHIP-14 scale than to the GOHAI scale. Thus, the OHIP-14 scale may be more useful in assessing OHRQoL in HD patients.

Social costs of loss in productivity-related absenteeism in Poland.

OBJECTIVES: The aim of this study was to estimate indirect costs associated with losses in productivity due to sickness absence among registered workers in Poland. MATERIAL AND METHODS: Data on sick leave durations in 2013 was obtained from the Social Insurance Institution (SII) (Zaklad Ubezpieczen Spolecznych - ZUS). Based on the number of assumptions, this data was used for calculating absence durations. The costs of lost productivity were estimated on the basis of the measure of gross value added. RESULTS: Estimated losses in productivity due to absenteeism in 2013 together accounted for 4.33% of gross domestic product (GDP) (17.09 billion euro). In the female population, the total value of losses amounted to 9.66 billion euro, but excluding the costs of pregnancy, childbirth, and puerperium (2.96 billion euro), it was 6.7 billion euro. In the male population, the loss amounted to 7.43 billion euro. The highest overall costs of sickness absence based on age were found in the age group of 30-39 years (5.14 billion euro, including pregnancy, childbirth, and puerperium - 1.474 billion euro; respiratory diseases - 0.632 billion euro, injuries and poisonings - 0.62 billion euro). In the group of people aged > 40 years, the highest cost was generated by bone-muscular diseases (1.553 billion euro) and injuries and poisoning (1.251 billion euro). Higher losses in the productivity of women in addition to pregnancy, childbirth, and puerperium were due to mental and behavioral disorders (0.71 billion euro), diseases of the genitourinary system (0.38 billion euro), and neoplasms (0.35 billion euro). At the same time, in men, compared to women, we observed higher losses due to injuries and poisoning (1.65 billion euro), and diseases of musculoskeletal (1.26 billion euro), nervous (0.79 billion euro), circulatory (0.65 billion euro), and digestive (0.41 billion euro) systems. CONCLUSIONS: Improvement and further development of effective strategies for prevention of complications of pregnancy and chronic diseases in the workplace are necessary. Policies aimed at reduction of sickness absence could potentially increase prosperity and the socioeconomic situation in Poland. Int J Occup Med Environ Health 2017;30(6):917-932.

[Treatment of hypertension in dialysis patients and renal transplant recipients]. / Leczenie nadcisnienia tetniczego u pacjentów dializowanych i po przeszczepieniu nerki.

Hypertension is often observed in dialysis patients and renal transplant recipients and is a very important risk factor for cardiovascular morbidity and mortality. Despite this high prevalence, the treatment of hypertension in these populations is poorly characterized. This article describes the current state of knowledge in treatment of hypertension in patients on renal replacement therapy. It is not appropriate, to limit the choice of drug to a single class of agents because people usually have other medical problems that affect this decision.