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In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p interaction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

Background Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8–6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

Background Disturbances in polyunsaturated fatty acids (PUFA) could predispose renal transplant (RTx) patients to cardiovascular risk. The purpose of this study was to evaluate serum content of ω-3 and ω-6 PUFA in RTx subjects, in comparison to nontransplanted chronic kidney disease (CKD) patients in predialysis stages and to healthy controls. In the second part of the study, PUFA were analyzed in subcutaneous adipose tissue of CKD subjects at the time of kidney transplantation. Methods The first part of the study was conducted in a cohort (n = 134) of 3 groups: patients after renal transplantation (RTx group, n = 24), patients with CKD in stages 2-5, not on dialysis (CKD-ND group, n = 67), and controls without CKD (control group, n = 43). The fatty acids (FA) assessed by gas chromatography-mass spectrometry (GC-MS) were alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). Diet was assessed by food frequency questionnaire FFQ-6. In the second part of the study, the same FA were evaluated in samples of adipose tissue taken during the kidney transplantation procedure and compared with FA of controls from the adipose tissue collected during hernia surgeries. Results The first part of the study showed that RTx patients presented significantly lower serum content of all the examined PUFA, in comparison to the CKD-ND group and controls. For instance, EPA in RTx equaled 0.65 ± 0.32%, in CKD-ND 0.82 ± 0.43%, and in controls 1.06 ± 0.68% (P = .005). No significant correlations were found between serum PUFA and diet in RTx patients. The second part of the study revealed no significant difference in the adipose tissue PUFA between CKD patients at the time of kidney transplantation and controls. Conclusions RTx patients present with low serum content of potentially beneficial PUFA. This finding does not seem to be solely due to an altered diet. Observed disorders might result from immunosuppressive drugs or other, yet undetermined, causes.

We sought to identify patients with amyotrophic lateral sclerosis (ALS) who displayed suspected peripheral nervous system (PNS) inflammation to compare them to those with suspected PNS degeneration.We measured sonographic median and ulnar nerve cross-sectional area (CSA) and cerebrospinal fluid albumin/serum albumin ratio (Qalb ) in patients with ALS to classify them as having suspected PNS degeneration (small CSA/low Qalb ) or inflammation (larger CSA/high Qalb ).Fifty-seven percent of patients had suspected PNS degeneration, 21% had suspected PNS inflammation, and 21% displayed suspected 'normal PNS state.' Suspected PNS degeneration was related to classic ALS, shorter disease duration, and a smaller hypoechoic nerve area. Suspected PNS inflammation was associated with men, longer disease duration, and a larger hypoechoic nerve area and was the dominant finding in superoxide dismutase 1 mutation carriers.Our simple approach might aid in the in vivo differentiation of supposed ALS subtypes, those with suspected PNS degeneration vs. inflammation, for stratification in clinical trials. Muscle Nerve 59:567-567, 2019.

These guidelines follow the mission of the World Association of Perinatal Medicine, which brings together groups and individuals throughout the world with the goal of improving outcomes of maternal, fetal and neonatal (perinatal) patients. Guidelines for auditing, evaluation, and clinical care in perinatal medicine enable physicians diagnose, treat and follow-up of COVID-19-exposed pregnant women. These guidelines are based on quality evidence in the peer review literature as well as the experience of perinatal expert throughout the world. Physicians are advised to apply these guidelines to the local realities which they face. We plan to update these guidelines as new evidence become available.

Patients with end-stage kidney disease, treated with renal transplantation, are at increased risk of cardio-vascular disease (CVD) and cardio-vascular mortality. They are also characterized by an atherogenic dyslipidemia. Alterations of the fatty acids (FA) profile contribute to increased cardio-vascular risk in the general population. In the current study, we test the hypothesis that kidney transplantation is associated with ab-normalities in FA profile. The FA profile was analyzed by gas chromatography–mass spectrometry in 198 renal transplant recipients, and 48 control subjects. The most profound differences between renal transplant patients and controls were related to the content of branched chain FA, monounsaturated FA, and n-6 polyunsaturated FA, respectively. The FA profile significantly separated the patients from the controls in the principal component analysis (PCA). The abnormalities of FA profile showed a tendency for normalization in long-term kidney recipients, as compared to patients with recent transplants. The n-3 PUFA content demonstrated a strong inverse association with the presence of inflammation. Most profound alterations of the FA profile were observed in patients with impaired graft function (glomerular filtration rate &lt, 45 mL/min). The study demonstrated significant disorders of the FA profile in kidney transplant recipients, which might contribute to cardio-vascular risk in this vulnerable patient population.

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive, neurodegenerative disorder affecting upper and lower motor neurons. Approximately 10% of patients suffer from familial ALS (FALS) with mutations in different ubiquitously expressed genes including SOD1, C9ORF72, TARDBP, and FUS. There is compelling evidence for mitochondrial involvement in the pathogenic mechanisms of FALS and sporadic ALS (SALS), which is believed to be relevant for disease. Owing to the ubiquitous expression of relevant disease-associated genes, mitochondrial dysfunction is also detectable in peripheral patient tissue. We here report results of a detailed investigation of the functional impairment of mitochondrial oxidative phosphorylation (OXPHOS) in cultured skin fibroblasts from 23 SALS and 17 FALS patients, harboring pathogenic mutations in SOD1, C9ORF72, TARDBP and FUS. A considerable functional and structural mitochondrial impairment was detectable in fibroblasts from patients with SALS. Similarly, fibroblasts from patients with FALS, harboring pathogenic mutations in TARDBP, FUS and SOD1, showed mitochondrial defects, while fibroblasts from C9ORF72 associated FALS showed a very mild impairment detectable in mitochondrial ATP production rates only. While we could not detect alterations in the mtDNA copy number in the SALS or FALS fibroblast cultures, the impairment of OXPHOS in SALS fibroblasts and SOD1 or TARDBP FALS could be rescued by in vitro treatments with CoQ10 (5 μM for 3 weeks) or Trolox (300 μM for 5 days). This underlines the role of elevated oxidative stress as a potential cause for the observed functional effects on mitochondria, which might be relevant disease modifying factors.

Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

The increased risk of atherosclerosis in patients with chronic kidney disease (CKD) is associated with the increased concentration of fatty acids from the omega-6 family. Products of arachidonic acid oxidation, including prostaglandins, thromboxanes, hydroxyleicosa-tetraenoic acids (HETES) and hydroxyoctadecadienoic acids (HODES) are involved in the pathogenesis of cancer and cardiovascular diseases due to increased oxidative stress. The aim of our study was to determine the relations resulting from the duration of CKD treatment. One of our main concerns is, whether and when the cascade of synthesis of inflammatory mediators may be insufficient in patients with CKD during many years of treatment. The study involved 121 patients with CKD and 87 healthy volunteers. Eicosanoid profiles 9(S)-HODE, 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R)-lipoxinA4, 5(S),6(R),15(R)-lipoxinA4 were extracted in plasma. The HPLC separations were performed by means of 1260 liquid chromatography. Patients with CKD have a significantly higher concentration of the following inflammatory mediators: 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R), 15(R)-lipoxinA4 relative to the control group. However, the concentrations of 9(S)-HODE were lower in the CKD group. The comparison of sexes did not show significant differences in terms of CKD. A tendency for lower concentrations of HETE and HODE were observed in the group of men. 15LOX, 12LOX and 5LOX pathways in chronic kidney disease are increased, while COX are suppressed (9-HODE). The analysis of the treatment time of patients with CKD shows that incorrect levels of 5(S), 6(R) and 15(R)-lipoxinA4 are developed. We present a new evidence of possible concepts and future clinical interventions in patients suffering from chronic kidney disease for many years. These data for the first time demonstrate that lipoxin levels drastically decrease in the course of CKD. Therefore, synthetic LXA4 analogues may be used as an antioxidant therapy in CKD, which requires further research.

Background Renin-angiotensin system (RAS) blocking agents efficiently control hypertension in renal transplant recipients (RTRs), and reduce proteinuria and post-transplant erythrocytosis. A beneficial effect on the retardation of the long-term decline in renal function has not yet been demonstrated. The aim of the study was to evaluate the effects of RAS blockade on allograft function. Methods In order to minimize donor variability and bias, 33 pairs of RTRs receiving grafts from the same donor were included into the retrospective analysis. A total of 66 RTRs were enrolled in which 1 patient from the pair used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a minimum period of 60 months (RAS[+]) and the second one did not use it at all (RAS[-]). Results There were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, mismatches number, duration of total ischemia, episodes of cytomegalovirus infections, acute rejections, or immunosuppressive treatment. Significantly, more RAS(+) patients presented with diabetes and cardiovascular complications. Among RAS(+) patients, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in 28 (84.84%) and 5 (15.15%) patients in a mean dose of 23.03 ± 16.83% and 30 ± 11.18% of their maximum doses, respectively. There were no significant differences in estimated glomerular filtration rate changes (−0.37 ± 12.68 vs 2.54 ± 20.76 mL/min) and serum creatinine changes (0.05 ± 0.39 vs 0.14 ± 0.79 mg/dL) between RAS(+) and RAS(-) patients during the 60 months follow-up. Conclusion Agents inhibiting the RAS did not significantly affect graft function in RTRs during 60 months of observation.

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.

Introduction: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS). Methods: In 37 patients, ulnar and median nerve cross-sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow-up was 14.5 months. Linear mixed-effects models were conducted to analyze time effects on CSA. Results: Ulnar nerve CSA declined significantly at a monthly rate of –0.04 mm (forearm) and –0.05 mm (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA. Conclusions: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391–397, 2016.

Bioenergetic failure, oxidative stress, and changes in mitochondrial morphology are common pathologic hallmarks of amyotrophic lateral sclerosis (ALS) in several cellular and animal models. Disturbed mitochondrial physiology has serious consequences for proper functioning of the cell, leading to the chronic mitochondrial stress. Mitochondria, being in the center of cellular metabolism, play a pivotal role in adaptation to stress conditions. We found that mitochondrial dysfunction and adaptation processes differ in primary fibroblasts derived from patients diagnosed with either sporadic or familial forms of ALS. The evaluation of mitochondrial parameters such as the mitochondrial membrane potential, the oxygen consumption rate, the activity and levels of respiratory chain complexes, and the levels of ATP, reactive oxygen species, and Ca2+ show that the bioenergetic properties of mitochondria are different in sporadic ALS, familial ALS, and control groups. Comparative statistical analysis of the data set (with use of principal component analysis and support vector machine) identifies and distinguishes 3 separate groups despite the small number of investigated cell lines and high variability in measured parameters. These findings could be a first step in development of a new tool for predicting sporadic and familial forms of ALS and could contribute to knowledge of its pathophysiology.-Walczak, J., Debska-Vielhaber, G., Vielhaber, S., Szymanski, J., Charzynska, A., Duszynski, J., Szczepanowska, J. Distinction of sporadic and familial forms of ALS based on mitochondrial characteristics.

Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33-83) years, 61% male, disease duration 10 (0.2-190) months] and 33 age- and sex-matched disease controls [60 (32-76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared to controls [8343 (1795-35,945) pg/ml vs. 1193 (612-2616), H(1) = 70.8, p

Objective We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS). Methods The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined. Results In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered. Conclusions This systematic study confirmed a long-observed physical examination finding in ALS – weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration. Significance In ALS, dissociated forearm muscle weakness could aid in the disease’s diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength.

We aimed to investigate whether sonographic peripheral cross-sectional nerve area (CSA) and progranulin (PGRN), a neuritic growth factor, are related to each other and whether they interact to predict clinical and paraclinical measures in amyotrophic lateral sclerosis (ALS).We included 55 ALS patients who had forearm median and ulnar nerve CSA, cerebrospinal fluid (CSF) PGRN, and serum PGRN measures available. CSF PGRN was normalized against the CSF / serum albumin ratio (Qalb ). Using age, sex, height, and weight adjusted general linear models, we examined CSA × CSF PGRN interaction effects on various measures.There was a medium-effect size inverse relationship between CSA and CSF PGRN, but not between CSA and serum PGRN. Lower CSA values together with higher CSF PGRN levels were linked to smaller motor amplitudes.In ALS, the constellation of peripheral nerve atrophy together with higher CSF PGRN levels indicates pronounced axonal damage. Muscle Nerve 57: 273-278, 2018.

Background There is considerable controversy over the benefits of renin-angiotensin system (RAS) blockade in renal transplant recipients (RTRs). The aim of the study was to research the effects of RAS blockade on allograft and patient outcome. Methods A retrospective analysis of the effects of RAS blockade on allograft and patient outcome in 53 pairs of RTRs receiving grafts from the same donor was performed. The 106 RTRs (53 pairs), transplanted from 2002 to 2012, were included in the study when 1 patient from the pair used an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for a minimum period of 36 months (RAS[+]) and the second one did not use it (RAS[−]). Results There were no differences between RAS(+) and RAS(−) subjects in terms of age, body mass index, reason of end-stage renal disease, mismatches number, total ischemic time, episodes of cytomegalovirus infections, acute rejections, and immunosuppressive treatment. The mean time of observations was 66.28 months ± 24.39 months. RAS inhibitors were given in a mean dose of 23.1% (ACEI) and 27.08% (ARB) of the maximum recommended. The main reasons for the therapy were as follows: hypertension (39.62%), nephroprotection/proteinuria (39.62%), and polyglobulia (28.3%). The composite cardiorenal endpoint was reached by 6 (11.32%) and 7 (13.21%) patients in RAS(+) and RAS(−) group, respectively. There were no differences in changes of creatinine, potassium serum level, or estimated glomerular filtration rate between RAS(+) and RAS(−) patients in the early period after RAS blockade commencement. Conclusion Agents inhibiting the RAS system neither improved nor deteriorated patients and graft survival in RTRs.

Background: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. We performed a double-blind, placebo and losartan controlled, cross-over study to evaluate the influence of aliskiren, direct renin inhibitor on albuminuria and other surrogate markers of kidney injury in patients after renal transplantation. The safety of this therapy was also evaluated. Method: 16 of 18 patients (12M, 4F), 48.3 ± 9.0 years, 57.7 ± 9.1 months after kidney transplantation, with hypertension and stable serum creatinine 1.4±0.08 without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with aliskiren 150 mg and one with losartan 50 mg) in random order, allowing an 8-week placebo washout between them. Results: Aliskiren decreased 24h systolic and 24h diastolic blood pressure as compared to placebo (post hoc: p=0.009 and p=0.003). Aliskiren decreased albuminuria more effectively than placebo as well (post hoc: p=0.032). There were no differences between aliskiren and losartan in these regards. The influence of aliskiren on N-acetyl-β-D-glucosaminidase, transforming growth factor β-1 and 15-F2t-isoprostanes urine excretions was not significant. Serum potassium, creatinine, eGFR and trough blood cyclosporine or tacrolimus level were unaffected. A significant but not clinically relevant decrease in haemoglobin level after aliskiren was observed. Conclusion: Aliskiren decreases albuminuria in renal transplant recipients with clinically minimal side effects.

Background There are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC). Methods The study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4. Results Ki-67 ≥14% (hazard ratio [HR] 2.76; P P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 ( P Conclusions ER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.

Purpose In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient’s sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account. Methods The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb. Results In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p

In the PI(3,5)P2 biosynthetic complex, the lipid kinase PIKFYVE and the phosphatase FIG4 are bound to the dimeric scaffold protein VAC14, which is composed of multiple heat-repeat domains. Mutations of FIG4 result in the inherited disorders Charcot-Marie-Tooth disease type 4J, Yunis-Varon syndrome, and polymicrogyria with seizures. We here describe inherited variants of VAC14 in two unrelated children with sudden onset of a progressive neurological disorder and regression of developmental milestones. Both children developed impaired movement with dystonia, became nonambulatory and nonverbal, and exhibited striatal abnormalities on MRI. A diagnosis of Leigh syndrome was rejected due to normal lactate profiles. Exome sequencing identified biallelic variants of VAC14 that were inherited from unaffected heterozygous parents in both families. Proband 1 inherited a splice-site variant that results in skipping of exon 13, p.Ile459Profs(∗)4 (not reported in public databases), and the missense variant p.Trp424Leu (reported in the ExAC database in a single heterozygote). Proband 2 inherited two missense variants in the dimerization domain of VAC14, p.Ala582Ser and p.Ser583Leu, that have not been previously reported. Cultured skin fibroblasts exhibited the accumulation of vacuoles that is characteristic of PI(3,5)P2 deficiency. Vacuolization of fibroblasts was rescued by transfection of wild-type VAC14 cDNA. The similar age of onset and neurological decline in the two unrelated children define a recessive disorder resulting from compound heterozygosity for deleterious variants of VAC14.

Molecular analysis of dermatophytes (based on PCR fingerprinting) revealed high clonal differentiation between the genus and species. Microsporum canis (zoophilic dermatophyte, belonging to genus Microsporum), responsible for most cases of tinea capitis in children, tinea corporis in adults and dermatophytoses in cats, is very unique in comparison with other dermatophytes. Results of most molecular studies show that there is no clonal differentiation within M. canis as distinct from other species. The aim of this study was application of (GACA)4 repetitive primer and (ACA)5 primer for typing of M. canis strains isolated from human and animals in Central Poland. Fungal strains: 32 clinical isolates of M. canis, originated from patients from Central Poland; 11 strains isolated from infected cats (6) and dogs (7), reference strains of M. canis (CBS 113480), T rubrum (CBS 120358), T mentagrophytes (CBS 120357) and E. floccosum (CBS 970.95). The genomic DNAs of the strains were used as a template in RAPD reaction. No differentiation was observed for the analyzed M. canis strains using (GACA)4 and (ACA)5 typing.

Although individuals with end-stage renal disease (ESRD) who receive maintenance dialysis often present with memory deficits, the nature of this impairment remains controversial. Thus, this study was aimed to better characterize memory functioning of dialyzed patients and to identify potential predictors of their memory performance. A total of 61 dialyzed patients with ESRD and 30 demographically matched normal controls (NC) were the participants for this study. Overall, individuals with ESRD obtained significantly lower memory scores than NCs. Moreover, the pattern of their performance was consistent with that of subcortical cerebrovascular disease. Additionally, our results indicate that age, years of education and premorbid intelligence, depression symptoms, and blood urea nitrogen, as well as a history of coronary artery bypass grafting (CABG), are significant predictors of memory performance of adequately dialyzed patients with ESRD. Importantly, when the presence of CABG was controlled, the memory performance of dialyzed patients did not significantly differ from that of NCs.

Herein we have reported the use of rapamycin in immunosuppressive treatment after renal transplantation as a therapy of choice in a patient with diagnosis of tuberous sclerosis complex (TSC). TSC is a genetic disorder, caused by mutations of TSC1 or TSC2 genes. Products of these genes, hamartin and tuberin, create a complex that inhibits mammalian target of rapamycin (mTOR), a key protein engaged in regulation of the cell cycle. Mutations of TSC genes lead to constitutive activation of mTOR resulting in uncontrolled proliferation, differentiation, and migration of cells. As a consequence malformations of many organs arise. We have presented a case of a 47-year-old female TSC patient with multisystem involvement (skin, brain, lungs, and kidneys), who developed end-stage renal disease ESRD due to angiomyolipomas with subsequent bilateral nephrectomy. At the age of 44 years, she started hemodialysis treatments and 10 months later underwent kidney transplantation. Immunosuppressive treatment included the mTOR inhibitor rapamycin. Since the patient was discharged from hospital, she has remained in good clinical condition with stable graft function. Clinical evaluation after 2 years treatment with rapamycin revealed significant regression of skin lesions. Brain, chest, and abdominal cavity computed tomography images remained stable. No complications of immunosuppressive treatment or TSC were observed. Experimental and clinical studies have confirmed that rapamycin exerts beneficial effects in TSC, providing a new therapeutic option. Therefore an immunosuppressive regimen with rapamycin should be considered as the treatment of choice after kidney transplantation among patients with TSC seeking to avoid development or progression of disease complications.

Death with a functioning kidney is the most frequent cause of graft failure. Cardiovascular disease is the most frequent cause of death after renal transplantation. Therefore, prior to grafting, it is mandatory to diagnose and treat coronary artery disease and heart valve impairment. Transplantation is the best option for renal replacement therapy as far as the quality of life and life expectancy are concerned, although patients with such comorbidities may experience a higher short-term mortality risk. The objective for this study was to analyze both short- and long-term results of patients after coronary artery bypass grafting (CABG) or cardiac valve replacement (CVR). The cardiac surgery recipient group (CSR) included 16 patients (15 men, 1 woman) aged from 44 to 73 (mean 54.9 ± 7.8) years. CABG was performed in 13/16 patients, and CVR in 3/16. The rest of our patients were treated as a comparative noncardiac surgery recipient (non-CSR) group. It consisted of 422 patients (264 men, 158 women) aged from 14 to 68 years (mean 43.2 ± 12.9). The comparison revealed that graft function estimated at 1 year after transplantation was not different: serum creatinine concentrations of 1.7 ± 0.2 and 1.6 ± 0.5 mg/dL in CSR and non-CSR, respectively. One-year patient survival in the CVR group of 93.8% was slightly worse than that in the non-CSR group (97.9%), but death-censored 1-year graft survivals were comparable in both groups (93.8% vs 92%). Urinary tract and cytomegalovirus infections were the most common complications in the CSR group. One patient lost his graft in month 3rd due to many serious infectious complications. One patient died at the end of 12 months as a result of a cardiovascular event (1/16). Our single-center results confirm that transplantation in patients after CABG or CVR is a safe procedure; therefore, such patients should be referred into the waiting list.

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.

Background Increasing evidence shows that body mass may play a role in complications after kidney transplantation and influence graft and patient survival. The aim of this study was to analyze the association between graft function and both the body mass and adipokines (leptin, visfatin, adiponectin) in kidney transplant recipients. Methods We studied 183 kidney transplant recipients from the Department of Nephrology, Transplantology and Internal Disease, Medical University of Gdansk. Anthropometry and body composition examinations were performed using an electronic scale, hand grip dynamometer, and BCM - Body Composition Monitor (Fresenius, Germany). Obesity, overweight, and underweight were defined according to body mass index (BMI) classification. Blood urea nitrogen, creatinine, blood morphology, lipidogram, albumin, and C-reactive protein were measured. Estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula. Leptin, visfatin, and adiponectin were measured by ELISA methods. Results Underweight was found in 16 (8.7%) KTR, overweight and obesity were observed in 68 (37.1%) and 26 (14.2%) patients, respectively. No relation between BMI and eGFR in all groups was noted, but in the early period after transplantation a correlation between BMI and creatinine and eGFR was observed. In all studied patients (also patients in the early posttransplantation period), eGFR significantly correlated with leptin and visfatin. Multiple regression analysis confirmed an association between eGFR and leptin and visfatin in all studied populations and between eGFR and BMI in the group examined shortly after transplantation. Conclusions Sarcopenic overweight and obesity prevail in KTR. In the short-term but not long-term period after transplantation, worse graft function was associated with high BMI. An association between graft function and leptin and visfatin was noted.

Summary Introduction In various countries, standard doses of anti-D IgG used for postpartum immunoprophylaxis of hemolytic disease of fetus and newborn (HDFN) vary from 100 μg to 300 μg. There are also different regulations concerning FMH assessment, and opinions about applicable tests are inconclusive. Methods Three flow cytometry tests (FCTs) with anti-D, anti-HbF, anti-HbF+CA antibodies, and two modifications of microscopic Kleihauer–Betke test (KBT) were used. Results In all artificial mixtures with known concentrations, FCTs and KBT with counting 10 000 RBCs had similar satisfying sensitivity and specificity. KBT with counting 2000 RBCs had to be disqualified because of significant discrepancies between expected and measured values of FMH. The test procedure with anti-D was easier and shorter than the remaining tests, but it can be only used for FMH assessment in RhD-negative mothers with RhD-positive newborns. In one clinical sample, it was impossible to distinguish fetal RBCs from maternal F cells in KBT and FC with anti-HbF but other tests were useful. Conclusion In the four tests, correlation between expected and obtained results was appropriate (CCC 1). Each test had some advantage and limitation in any clinical situation. Therefore, it is best to have opportunity to perform two or three assays in the laboratory.

Background Ozonated autohemotherapy (O 3 -AHT) is a clinically useful therapeutic procedure in hemodialyzed patients with peripheral arterial occlusive disease (PAOD). The majority of patients on dialysis are in a hypercoagulable state. Thrombotic complications are the major cause of morbidity and mortality in hemodialyzed patients. Effects of O 3 -AHT on blood coagulation were evaluated in 11 hemodialyzed patients affected by PAOD. Methods We performed an oxygen-controlled, crossover study in which nine sessions of autohemotherapy with oxygen administration (AHT) as a control were followed by nine sessions of O 3 -AHT. Blood coagulation was assessed by antithrombin III, activated partial thromboplastin time, prothrombin time, D-dimer and fibrinogen plasma concentrations. Results The extents of all the measured parameters after nine sessions of O 3 -AHT did not differ statistically from the values after nine sessions of AHT. Similarly, there were no differences in the measured variables after the first session of O 3 -AHT as compared to the values before therapy. We did not observe any thrombotic accidents during the study. Conclusions O 3 -AHT with ozone concentration of 50 μg/mL and citrate as an anticoagulant does not influence blood coagualation parameters in hemodialyzed patients with PAOD.

Objective The objective of our study was to evaluate whether bioelectrical impedance analysis (BIA) performed 15 minutes after a hemodialysis (HD) session is clinically useful in nutrition status assessment in comparison with BIA performed before HD. Because of better reliability, it is postulated in the literature that BIA measurements should be performed 1 to 5 hours after HD sessions. However, the measurements 1 to 5 hours after HD sessions are inconvenient in clinical practice. Furthermore, the currently published BIA reference values for the HD population are based on the measurements taken before HD sessions. Methods The study group consisted of 29 HD patients who were in a stable clinical condition. BIA measurements were performed by means of BIA 101 System (Akern RJL Systems, Florence, Italy). The correlation coefficients were surveyed between traditional indices of nutritional status, such as body mass index (BMI) and plasma concentrations of protein, albumin, and nonprotein nitrogen blood urea nitrogen (BUN) (measured before HD) on one hand, and BIA parameters (taken before and 15 minutes after HD) on the other hand. Results Statistically significant correlations occurred between such BIA parameters as (1) phase angle and BMI or albumin, or total protein or BUN and (2) body cell mass and BMI or BUN. The differences between correlation coefficients achieved either before or after HD were statistically nonsignificant. Conclusions BIA measurements in the studied group of patients did correlate with traditional indices of nutritional status. The correlation coefficients were not significantly influenced by the time of performing BIA measurements. The obtained correlations confirm that BIA performed 15 minutes after an HD session may be a useful tool in evaluation of nutritional status of stable HD patients in clinical practice.

To evaluate cerebral metabolism and intergroup differences in closely matched patients with myotonic dystrophy type 2 (DM2, n = 15) and type 1 (DM1, n = 14), we performed 1H magnetic resonance spectroscopic (MRS) analyses of the occipital and temporoparietal cortical regions as well as of subcortical frontal white matter. Relative to healthy subjects, the concentration of N-acetylaspartate was significantly reduced in all tested brain regions in both disease groups. In the DM1 patients we also observed a concomitant depletion of creatine and choline levels, particularly in the frontal white matter. A discriminant analysis based on the 1H-MRS data distinguished between the DM2, DM1, and control groups with an overall accuracy of 88%. 1H-MRS indicates that neurochemical alterations involving gray and white matter occur in patients with DM2 and DM1. Although structural abnormalities (cerebral atrophy, white matter lesions) are similar in DM2 and DM1, changes in cerebral metabolites can differentiate these disease groups, suggesting that the diseases differ in their neurocellular pathology. Muscle Nerve, 2006

The purpose of this study was to determine the effects of a successful renal transplantation on left ventricular (LV) morphology, systolic and diastolic function. Forty-three renal transplant patients prospectively studied by echocardiography (30 months follow-up) were divided into two groups. The first echocardiographic examination was performed 3.0 +/- 2.8 months after renal transplantation in group I (11 men, 12 women); and 34.4 +/- 29.1 months after transplant in group two (9 men, 11 women). We noticed the following changes in blood pressure (BP): group 1 systolic BP reduction (from 140.5 +/- 23.6 to 126 +/- 6.8 mmHg; P.01), and pulse pressure reduction (from 59.5 +/- 14.9 to 47.5 +/- 9.8 P.05); group 2, diastolic BP acceleration (from 78.4 +/- 8.7 to 84 +/- 6.9 mmHg, P.05). LV mass index decreased in group 1 (from 126.4 +/- 18.0 g/m2 to 104.6 +/- 15.9 g/m2, P.05). The incidence of LV hypertrophy (LVH) decreased in group 1 from 70% to 40% (P.05). Only one parameter of systolic function-end systolic stress-significantly decreased in both groups: group 1 from 78 +/- 11 to 61 +/- 12 g/cm2; group 2 from 63.8 +/- 9.0 to 55.1 +/- 9.0 g/cm2, P.05). The pattern of mitral inflow changed: in group 1, the normal pattern decreased from 30% to 20% and the restrictive pattern increased from 0% to 10%; in group 2, the normal mitral inflow pattern decreased from 60% to 20% and abnormal relaxation type increased from 40% to 80%. Regression of LVH after renal transplant improved LV geometry and systolic function. Despite better systolic function a progression of LV diastolic dysfunction was noticed, which might be explained by cyclosporine treatment. Renal transplantation exerted a beneficial impact on cardiomyopathy manifested by LVH and systolic dysfunction.

Background The therapeutic use of ozone is still a controversial medical strategy due to the potential toxicity of ozone, which is recognized as a highly reactive oxidant. The reactive oxygen species are known to induce platelet aggregation, the process involved in the development of atherosclerosis and cardiovascular events. In the present study, the influence of ozonated autohaemotherapy (O 3 -AHT) on the platelet function was evaluated in chronically haemodialysed patients with peripheral arterial disease. Methods This was an oxygen-controlled, cross-over study, in which nine sessions of autohaemotherapy with oxygen administration as a control were followed by nine sessions of O 3 -AHT. The platelet function was assessed by the extent of spontaneous aggregation (SPA) and agonist-induced aggregation (AIPA), where different concentrations of adenosine were used as an agonist Results There were no differences between SPA and AIPA assessed after nine sessions of O 3 -AHT and after nine sessions of autohaemotherapy with oxygen administration. SPA and AIPA did not change after the first session of O 3 -AHT as compared with the levels before this procedure. Conclusion O 3 -AHT with ozone concentration of 50 μg/ml and citrate as an anticoagulant does not induce platelet aggregation.

There are a variety of complications related to chronic hemodialysis treatment, including thrombosis in hemodialysis access leading to blood recirculation, and in turn to the deterioration in hemodialysis effectiveness. Given that ozone decreases blood viscosity, increases erythrocyte deformability, and inhibits coagulation, the periodic blood ozonation may be of benefit in the attenuation of these disturbances. To gain insight into this issue, we originally evaluated the impact of ozonated autohemotherapy on recirculation in arteriovenous fistula, hemodialysis adequacy, and the frequency of dialyzer reuse. Twelve chronically hemodialyzed patients with peripheral arterial disease were enrolled in the prospective, placebo-controlled study. Nine sessions of autohemotherapy with the exposure of blood to oxygen, as a control, and nine sessions of autohemotherapy where the blood is exposed to ozone in a concentration of 50 µg/mL are administered in a single-blind manner. Access recirculation is measured by means of spectral technology (Crit Line Monitor, HemaMetrics, Kaysville, UT, U.S.A.), and hemodialysis adequacy is calculated using the Dau-girdas formula and expressed as the Kt/V index. The Kt/V index and the frequency of dialyzer reuse do not change after ozonated autohemotherapy. Recirculation decreases after ozonotherapy in the majority of patients, on average by 35.3%, but the change does not reach the level of statistical significance (P = 0.064). We demonstrate that ozonated autohemotherapy does not influence dialysis adequacy and the frequency of dialyzer reuse. The improvement of fistula function, expressed as a decrease in recirculation, is not significant, although seen in the majority of patients.

Ozonated autohemotherapy (O3-AHT) is used in the treatment of atherosclerotic ischemia of lower limbs (AILL). The impact of ozone on serum lipids and endothelium injury is of particular interest since these factors are important in the development of atherosclerotic lesions. To evaluate this issue, a prospective, placebo-controlled study was designed. Twelve hemodialyzed subjects with AILL received autohemotherapy with oxygen as a control followed by O3-AHT with ozone concentration of 50 micro g/ml. Serum lipids and plasma activity of von Willebrand factor (vWF) were measured. After O3-AHT, total cholesterol significantly decreased compared to the baseline (-8.34%) [P < 0.01]. LDL cholesterol was also significantly lower than the initial value (-17.71%) [P < 0.001]. No significant changes in the activity of vWF were found after the first session of O3-AHT and after all nine sessions of O3-AHT. The study demonstrated that O3-AHT did not affect deleteriously the endothelium in patients with chronic renal failure on maintenance hemodialysis. It may stimulate beneficial changes in serum lipid profile manifesting as a decrease in the total- and LDL-cholesterol levels.

Hemolysis after renal transplantation in some cases is clearly related to hemolytic-uremic syndrome (HUS) and usually attributed to cyclosporine (CsA) treatment. Acute hemolysis in other recipients is related to anti-erythrocyte autoantibodies. In most cases these patients have received ABO-compatible, although ABO-nonidentical, organs, mostly from O blood group donors. We report three cases of autoimmune hemolytic anemia after renal transplantation. Two patients (patients: 1 and 2; ABO-compatible, but nonidentical kidneys) suffered acute hemolysis in the third week after transplantation. One patient (patient 3: ABO-identical kidney) suffered a chronic, subclinical course of disease beginning 5 months after transplantation. The clinical picture of this disease was completely different from HUS. The existence of severe anemia (patients 1 and 2), hyperbilirubinemia (particularly high in patient 3), increased serum lactic dehydrogenase levels, and decreased serum haptoglobin in the presence of good graft function suggested an hemolytic anemia. In all patients the direct antiglobulin test was positive. The acute or chronic symptoms of hemolysis disappeared, at 2 and 5 weeks, respectively, after conversion from CsA to tacrolimus. Hemolysis in these patients probably relates to alloantibodies derived from passenger B lymphocytes transplanted with the organs. Because hemolysis has been most frequently related to CsA therapy, it is suggested that B lymphocytes proliferated and produced antibodies because CsA effects to inhibit T-cell function generally spares B-cell activity. It is proposed that a subtype of B cells, which are resistant to CsA, produces anti-A and/or anti-B antibodies. Treatment with tacrolimus appears to be successful, probably due to its alternate, and likely more effective, manner of B-cell suppression.

Renal transplant recipients (RTRs) are predisposed to fungal infections because of long-term graft-preserving immunosuppressive therapy.We prospectively enrolled 223 consecutive adult RTRs. Patients were transplanted at 1 of 2 transplant centers in Poland. The group consisted of 97 women (43%) and 126 men (57%). The control group consisted of 100 patients (39 women and 61 men) randomly selected from the outpatient dermatology clinic and from hospital personnel. All RTRs and the control group were screened for the presence of superficial fungal infections. All patients were examined by the same dermatologist. The oral mucosa and the entire body surface were fully examined. Mucosal swabs were obtained from all patients in both the examined and control groups. Skin scrapings and swabs were obtained from any clinically suspicious lesions. Nail clippings were collected in the case of any nail changes.Superficial fungal infections have been detected in 133 RTRs (60%)and 27 controls (27%; P = .00001). One hundred eight RTRs (62%) developed superficial fungal infections in the first year after transplantation (P.008). The most common site for superficial fungal infections in the RTRs group was the oral cavity. Candida albicans was the most frequently isolated species in the oral cavity.Superficial fungal infections in RTRs are statistically more common among RTRs than in the general population. Whether the drug was used separately or administrated under immunosuppressive combinations had no influence on the occurrence of fungal infections. The final results showed no correlation between patient age and the occurrence of fungal infections. Dermatologists who care for transplant patients should be aware of the clinical course of fungal species in RTRs compared with the general population.

Background Obesity and disturbances of adipokine concentrations are often recognized in kidney transplant recipients (KTRs). Leptin plays a key role in regulating energy intake and expenditure, including appetite and hunger, metabolism, and behavior. Adiponectin modulates certain metabolic processes, including glucose regulation and fatty acid oxidation, and exerts some weight-reduction effects. Visfatin has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptors and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. The aim of this study was to evaluate the prevalence of leptin, adiponectin, and visfatin and nutritional status abnormalities in stable KTRs. Methods Eighty KTRs aged 52.4 ± 14.0 years participated in the study. Nutritional status was determined with the use of the 7-point Subjective Global Assessment (SGA), anthropometric measurements (bioimpedance analysis), and serum concentration. Concentrations of leptin, adiponectin, and visfatin were measured with the use of enzyme-linked immunosorbent assay. Results Mean time after transplantation and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease formula) were 82.5 ± 56.5 months and 42.0 ± 15.0 mL/min/1.73 m 2 , respectively; 29 (36.2%) of the KTRs, despite high body mass index (BMI ≥25 kg/m 2 ), presented mild malnutrition (SGA ≤5). BMI, content of body fat, and leptin concentration correlated positively with time from transplantation and negatively with eGFR. Additionally, patients with BMI ≥25 kg/m 2 presented significantly higher leptin-to-adiponectin ratios compared with lean patients (3.5 vs 1.1, respectively; P 2 presented significantly lower leptin concentration and BMI. Conclusions Despite high BMI, mild malnutrition was present in one-third of KTRs. Increased BMI, abdominal obesity, and high leptin concentration were aggravated by time from transplantation and deterioration of graft function. Overweight/obesity and incorrect leptin-to-adiponectin ratio could increase cardiovascular risk in KTRs.

Introduction Overweight/obesity, malnutrition, and abnormalities in carnitine metabolism are recognized in kidney transplant recipients (KTRs). Aim The aim of this study was to evaluate the prevalence of nutritional abnormalities and carnitine status in KTRs. Methods The study was performed in 80 stable KTRs aged 52.4 ± 14.0 years, without carnitine supplementation. Nutritional status was determined using a 7-point Subjective Global Assessment, anthropometric measurements, and s-albumin level. Urinary excretion and serum concentration of total (TC), free (FC) carnitine were measured using enzymatic methods according to Cederblad. Results Mean transplantation vintage and estimated glomerular filtration rate (Modification of Diet in Renal Disease; 4 points) were 82.5 ± 56.5 months and 42.0 ± 15.0 mL/min/1.73 m2, respectively. Overweight and obesity were noticed in 41% and 14% of patients, respectively. Signs of malnutrition were present in 64% (21/33) of the overweight patients, and in 91% (10/11) of the obese patients. KTRs with malnutrition (Subjective Global Assessment ≤5) were significantly older, with longer transplantation vintage, lower eGFR, higher body mass index (BMI), higher body fat, and decreased hand grip strength in comparison to KTR with good nutritional status (Subjective Global Assessment >5). In 8.6% of KTRs, deficiency of FC (in serum and urine) was observed. Carnitine (TC and FC) and FC/TC ratio were not correlated with anthropometric and laboratory parameters of nutritional status. Serum of TC and FC concentrations negatively correlated with graft function. Conclusions Plasma carnitine deficiency (limited availability) can appear in the KTR group and does not correspond with signs of both malnutrition and obesity. In spite of overweight/obesity, KTRs showed features of malnutrition and they need thorough nutritional evaluation and appropriate nutritional interventions.

Background: FMH quantification is necessary to calculate an individual dose of prophylactic anti-RhD immunoglobulin and to diagnose fetal anaemia causes. We encountered a healthy woman with a numerous RBCs containing fetal haemoglobin (HbF). Aims: To investigate the cause of this sign and the correct evaluation of fetal RBCs in maternal circulation. Materials and Methods: Patient’s samples and artificial mixtures were tested by microscopic Kleihaur-Betke (KB) and flow cytometric (FC) tests with anti-HbF + anti-CA (carbonic anhydrase), and with anti-D. The patient’s blood count with reticulocyte parameters, and concentration of bilirubin, haptoglobin, iron, transferrin, ferritin, hepcidin, sTR, HbF, HbA2 were measured. Genes coding the β- and γ-globin were sequenced. Results: It was impossible to distinguish the population of fetal and maternal HbF positive cells using KBT and FC with anti-HbF. Application of anti-CA and anti-D allowed to separate them. Maternal blood haematological and biochemical parameters were normal but HbF was 3.3% of total Hb concentration (normal

In this study we sought to determine the cross-sectional area (CSA) of peripheral nerves in patients with distinct subtypes of amyotrophic lateral sclerosis (ALS).Ulnar and median nerve ultrasound was performed in 78 ALS patients [classic, n = 21; upper motor neuron dominant (UMND), n = 14; lower motor neuron dominant (LMND), n = 20; bulbar, n = 15; primary lateral sclerosis (PLS), n = 8] and 18 matched healthy controls.Compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS. Median nerve CSA (forearm/wrist level) did not differ between controls and ALS.Ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically, yet their accurate separation has major prognostic implications.

The excessive use of health care services by obese people constitutes a serious financial burden to all highly developed countries. As yet however, this has not been recognised to be a problem in Poland.To provide a preliminary analysis of Warsaw inhabitants in their use of and quality of received health care by comparing obese subjects with those of normal weight.Study subjects were fifty three obese (BMI30) and one hundred eighty one normal weight (18.5BMI25) inhabitants of Warsaw, who had taken part in a study on social participation in health care reforms. The use of health care services covered: visits to public health care physicians, hospitalisation and visiting private physicians. Assessing health care quality was by evaluating overall the health care system and the family doctor as well as out-of-pocket treatment expenses and any difficulties in accessing physicians.Obese subjects perceived their health to be significantly worse than those of normal weight and significantly more of them never attended private practice. Consultation with public health physicians was also frequently, but not significantly, higher in the former whilst hospital admissions were the same in both groups. Obese subjects gave considerably lower general assessments of the quality of the health care system and more often perceived their medical expenses as being very high, nevertheless, both these differences were statistically insignificant.The obtained findings have allowed us to formulate new recommendations for future research. These will examine various uses of health care services by the obese, i.e. family doctors and other specialists of public primary health care, out-patient clinic physicians and private physicians (according to their defined specialisations), hospitals according to location and rehabilitation centres. Account will be taken of visiting frequency, admission waiting time for physicians, length of visits, amounts of prescribed medication, out-of-pocket payment for treatment and medication, frequency of surgical interventions, satisfaction with given treatments and physician attitudes towards obese patients. Moreover, the socioeconomic status of the obese will be investigated as a potential obstacle to using health care services.

Bilateral nephrectomy for treatment of refractory hypertension in chronic hemodialyzed patients has been infrequently carried out. We analyzed the benefits of this operation on blood pressure, clinical state, drug treatment, and quality of life. In 10 hemodialyzed patients with refractory hypertension, systolic (SBP) and diastolic (DBP) blood pressure were measured 1 month before nephrectomy bilateral and 3, 6, 9, and 12 months after. In addition, the use of antihypertensive drugs before and after surgery was evaluated. Four patients had SBP and DBP values characteristic of malignant hypertension. In all 10 patients hypertension responded neither to reduction of plasma volume by ultrafiltration nor to multiple antihypertensive drug therapy. Hypertensive crises were associated with cerebral hemorrhage in two patients, severe encephalopathy with persistent neural dysfunction in one patient, and encephalopathy and diplopia in another. Three months after bilateral nephrectomy blood pressure decreased significantly (P < .005) and was normal in nine patients. In one noncompliant patient with intradialytic body weight increases of nearly 10%, blood pressure was still elevated. Malignant or drug-resistant hypertension with hypertensive crises is an indication for bilateral nephrectomy. The clinical state and quality of life improved in all patients in the present study and antihypertensive treatment is no longer necessary.

We present a successful pregnancy in a 37-year-old women with severe renal impairment due to medullary cystic disease. She presented five years earlier with hypertension and chronic renal failure with creatinine was 2.1 mg/dl (C cr 35 ml/min). She had had two successful pregnancies in the past, nine and seven years earlier. Diagnosis of medullary cystic disease (MCD) was made based on typical ultrasound appearance, sodium wasting and acidosis out of the proportion to the degree of renal failure. Over the next 5 years, a slow progression of chronic renal failure was observed with creatinine reaching 5.1 mg/dl (C cr 15,4 ml/min), shortly before she became pregnant in December 2001. Her hypertension remained well-controlled and serum creatinine decreased at the beginning of the second trimester to 3.7 mg/dl with subsequent increase toward the end of the pregnancy. She required increasing doses of erythropoietin and intravenous iron supplementation to maintain hemoglobin levels. The polyhydramnios developed necessitating five procedures of amnio reduction. She was not treated by dialysis. A boy weighing 1,600 g was delivered by cesarean section in the 35th week of gestation. The mother's creatinine rose to 5.2 mg/dl (C cr 15 ml/min) post partum and her renal function declined only slightly over the next 20 months. Our report illustrates that successful fetal and maternal outcome can be achieved even in cases of advanced renal failure preceding gestation. It appears that the type of renal disease influences the pregnancy course and outcome and thus should be considered in patient counseling and therapeutic decisions.

Obesity is well known cause of various diseases. However, there are only a few studies which enable to compare directly the magnitude of risk in different groups of chronic diseases.The aim of presented paper was to identify a magnitude of the risk of chronic diseases attributable to overweight and obesity on the basis of data on weight and height self-reported by respondents.The survey was conducted among 402 Warsaw inhabitants selected by non-random method. Overweight and obesity was measured by Body Mass Index (BMI) on the basis of the data of weight and height reported by respondents. According to WHO criteria the normal weight is defined as BMI 18.5 - 24.9 kg/m2, overweight as BMI 25.0 - 29.9 kg/m2, and obesity as BMI 30 kg/m2 or more. The following groups of chronic diseases were included: cancer, diabetes and other endocrine diseases, mental disorders, cardiovascular diseases, respiratory diseases, digestive diseases, arthritis and allergy disorder.Obesity measured by self-reported method was recognised as significant risk factor for diabetes (OR=9.6, CI: 2.0-152.8), respiratory diseases (OR=10.6, CI: 3,0-333,7), cardiovascular diseases (OR=5.2, CI: 1.9-108.3), arthritis (OR=6.3, CI: 2.4-266.7), digestive diseases (OR=3,8, CI: 1.3-83.6) and mental disorders (OR=5.8, CI: 1.5-29.1), while overweight significantly increased the risk of diabetes (OR=4.4, CI: 1.2-10.8), respiratory diseases (OR=3.2, CI: 1.4-22.2), cardiovascular diseases (OR=2.9, CI: 1.2-6.4) and arthritis (OR=3.0, CI: 1.1-9.6) CONCLUSIONS: Our findings showed that data on weight and height collected by survey method provide some information about the magnitude of the risk regarding particular groups of diseases attributable to overweight and obesity, nevertheless, underestimation of BMI calculated in this way should be taken into account.

The global economic crisis led to the need to reduce the public expenditure, including health care. In a situation of reduction of the publicly guaranteed benefits, some services may be available only in private physicians for particular patients. Therefore, there is a need to examine factors determining the use of both types of health care.The aim of the study was to assess the association between the use of free treatment of general practitioner and the use of private physician services on one hand, and health and its disorders, assessment of physician, and expenditure on treatment of the Warsaw inhabitants on other hand.The data were collected from 402 Warsaw inhabitants by not-addressed questionnaire elaborated in Health Promotion and Postgraduate Education Department of the National Institute of Public Health-National Institute of Hygiene.Our findings showed that the majority of respondents used the both types of health care. Males, people from the youngest and the oldest group, those having elementary education, students and unemployed were more likely to use only free treatment from general practitioner, whereas people aged 30-44 years, higher educated, employed and those depending on other people were more often treated only by private physicians. The beneficiaries of only private physician services higher evaluated their health, physically felt better, perceived stronger social support and rarely remained at home due to illness. Private physicians were evaluated more positively in comparison with general practitioner practicing in public health care, nevertheless, the difference was not large. With respect to their own financial situation, the people using private physician services did not find higher medical expenses than those using only the general practitioner of public health care. CONCLUSIONS. Our research indicates that uncontrolled development of private medical services market may increase inequality in access to health care, if not protected by appropriate access to public health care.

Charcot-Marie-Tooth neuropathy type 2A (CMT2A) is associated with heterozygous mutations in the mitochondrial protein mitofusin 2 (Mfn2) that is intimately involved with the outer mitochondrial membrane fusion machinery. The precise consequences of these mutations on oxidative phosphorylation are still a matter of dispute. Here, we investigate the functional effects of MFN2 mutations in skeletal muscle and cultured fibroblasts of four CMT2A patients applying high-resolution respirometry. While maximal activities of respiration of saponin-permeabilized muscle fibers and digitonin-permeabilized fibroblasts were only slightly affected by the MFN2 mutations, the sensitivity of active state oxygen consumption to azide, a cytochrome c oxidase (COX) inhibitor, was increased. The observed dysfunction of the mitochondrial respiratory chain can be explained by a twofold decrease in mitochondrial DNA (mtDNA) copy numbers. The only patient without detectable alterations of respiratory chain in skeletal muscle also had a normal mtDNA copy number. We detected higher levels of mtDNA deletions in CMT2A patients, which were more pronounced in the patient without mtDNA depletion. Detailed analysis of mtDNA deletion breakpoints showed that many deleted molecules were lacking essential parts of mtDNA required for replication. This is in line with the lack of clonal expansion for the majority of observed mtDNA deletions. In contrast to the copy number reduction, deletions are unlikely to contribute to the detected respiratory impairment because of their minor overall amounts in the patients. Taken together, our findings corroborate the hypothesis that MFN2 mutations alter mitochondrial oxidative phosphorylation by affecting mtDNA replication.

Self-rated health is a one-point measure commonly used for recognising subjectively perceived health and covering a wide range of individual's health aspects.The aim of our study was to examine the extent to which self-rated health reflects the differences due to demographic characteristics, physical, psychical and social well-being, health disorders, occurrence of chronic disease and negative life events in Polish social and cultural conditions.Data were collected by non-addressed questionnaire methods from 402 Warsaw inhabitants. The questionnaire contained the questions concerning self-rated health, physical, psychical and social well-being, the use of health care services, occurrence of chronic disease and contact with negative life events.The analysis showed that worse self-rated health increased exponentially with age and less sharply with lower level of education. Pensioners were more likely to assess their own health worse then employed or students. Such difference was not found for unemployed. Compared to married, the self-rated health of divorced or widowed respondents was lower. Gender does not differentiate self-rated health. In regard to well-being, self-rated health linearly decreased for physical well-being, for social and, especially, for psychical well-being the differences were significant, but more complicated. Hospitalisation, especially repeated, strongly determined worse self-rated health. In contrast, relationship between self-rated health and sickness absence or frequency of contact with physician were lower. Chronic diseases substantially increased the risk of poorer self-rated health, and their co-morbidity increased the risk exponentially. The patients with cancer were the group, in which the risk several times exceeded that reported for the patients of other diseases. Regarding negative life events, only experience with violence and financial difficulties were resulted in worse self-rated health.Our findings confirmed the usefulness of self-rated health for public health research.