LONG-TERM SURVIVAL OF THE TRANSPLANTED KIDNEY AND THE CLINICAL RELEVANCE OF DONOR-SPECIFIC ANTIBODIES

The aim of our study was to evaluate the relevance of donor-specific antibodies (DSA) as defined by solid-phase single-antigen (SA) assays for predicting long-term graft survival after kidney transplantation. Sera from 132 kidney transplant recipients were retrospectively tested before, 3, 6 and 12 months after transplantation. The incidence of rejection and graft survival was followed up for 7 years. We found 29 episodes of acute cellular rejection (CR), 21 cases of antibody-mediated rejection (AMR) and 18 graft failures due to immunological reasons. Pre-transplant DSA and DSA three months after transplantation correlated with an increased rate of AMR and impaired graft function. After the fourth year, recipients with persistent DSA were at a higher risk of graft failure (p = 0.0317). Antibody specificity was prevailingly to HLA class I antigens (66.6% DSA, 75% non-DSA). During the first year after transplantation, the number of patients with non-DSA decreased (30.3% to 10.7%), while, due to de novo production of antibodies, the number of DSA positive patients remained constant. Conclusion: Detection of antibodies to HLA antigens using solid-phase assays, especially single-antigen bead technology before and three months after transplantation is predictive for increased incidence of antibody-mediated rejection and impaired long-term kidney graft survival

Bronchoalveolar lavage cell profiles and proteins concentrations can be used to phenotype extrinsic allergic alveolitis patients

Abstract Background Extrinsic allergic alveolitis (EAA) patients form heterogenous group with different clinical manifestation and different prognosis. We aimed to determine how to phenotype distinct EAA subgroups. Predictive role of the bronchoalveolar lavage fluid (BALF) IL-4Rα concentration at the time of diagnosis with regard to the clinical behavior in EAA patients was studied. Methods Concentrations of MMP-7, IL-4Rα, TNF-α, and PAR-2 were measured in the BALF od 71 EAA patients at the time of diagnosis. Lung functions and outcome data were assessed at 12 months after the diagnosis. Correlations between the BALF protein concentration, cell profile, lung functions and patient outcome were determined. Results We found positive correlations between BALF IL-4Rα concentration and BALF eosinophils (p = 0,006), negative correlation between IL-4Rα BALF concentration and diffusing capacity (DLco) (p = 0,003), negative correlation between IL-4Rα BALF concentration and forced vital capacity (FVC) (p = 0,004) and negative correlation between IL-4Rα concentration and BALF lymphocytes (p = 0,04). The BALF concentration of IL-4Rα was significantly higher in acute exacerbation patients (p = 0,0032) and in patients progressing despite corticosteroid treatment (p = 0,04). We observed a positive correlation between MMP-7 BALF concentration and the BALF lymphocytes (p = 0.05), negative correlation between the PAR-2 BALF concentration and DLco (p = 0.04) and a negative correlation between the BALF TNF-α concentration and DLco (p = 0.03). Conclusions Specific subgroup of EAA patients with more severe functional impact, distinct BALF cell profile and higher IL-4Rα BALF concentration can be differentiated. Correlations between the BALF concentrations of PAR-2, MMP-7 and TNF-α with clinical parameters may reflect the role of inflammation in the pathogenesis of EAA

Polyclonal Anti-T-Cell Therapy for Type 1 Diabetes Mellitus of Recent Onset

The destruction of pancreatic β-cells in type 1 diabetes mellitus is mediated by autoreactive T-lymphocyte clones. We initiated a prospective randomized controlled trial of polyclonal rabbit anti-T-cell globulin (ATG) in patients with type 1 diabetes within 4 weeks of diagnosis and with residual post-glucagon C-peptide levels still over 0.3 nmol/l. ATG was administered as an initial bolus of 9 mg/kg followed by 3 consecutive doses of 3 mg/kg. An interim analysis was performed to establish whether any significant changes in C-peptide production and insulin requirement had occurred that would justify the continuation of this pilot study. By May 2004, 11 subjects were assigned to treatment with ATG along with intensified insulin therapy and 6 to intensified insulin therapy with placebo, and were followed for a period of at least 6 months. During the first 12 months a significant difference in the insulin dose trends was found between the groups (p = 0.010) with a lower insulin dosage in the ATG group. There was also a difference in the glucagon stimulated C-peptide level trends of marginal significance (p = 0.068). Compared to values at screening, stimulated C-peptide levels significantly improved in the ATG group (p = 0.012) but not in the placebo group. Complete diabetes remission occurred in 2 patients in the ATG and in none of the placebo group. Glycosylated hemoglobin at 12 months tended to be lower in the ATG group (p = 0.088). Significant adverse effects of ATG treatment, mainly transient fever and moderate symptoms of serum sickness (7 and 6 subjects, respectively) were observed during the first month only. The interim analysis of this ongoing study suggests that short-term ATG therapy in type 1 diabetes of recent onset contributes to the preservation of residual C-peptide production and to lower insulin requirements in the first year following diagnosis

Molecular Networks Involved in the Immune Control of BK Polyomavirus

BK polyomavirus infection is the important cause of virus-related nephropathy following kidney transplantation. BK virus reactivates in 30%–80% of kidney transplant recipients resulting in BK virus-related nephropathy in 1%–10% of cases. Currently, the molecular processes associated with asymptomatic infections in transplant patients infected with BK virus remain unclear. In this study we evaluate intrarenal molecular processes during different stages of BKV infection. The gene expression profiles of 90 target genes known to be associated with immune response were evaluated in kidney graft biopsy material using TaqMan low density array. Three patient groups were examined: control patients with no evidence of BK virus reactivation (n=11), infected asymptomatic patients (n=9), and patients with BK virus nephropathy (n=10). Analysis of biopsies from asymptomatic viruria patients resulted in the identification of 5 differentially expressed genes (CD3E, CD68, CCR2, ICAM-1, and SKI) (P<0.05), and functional analysis showed a significantly heightened presence of costimulatory signals (e.g., CD40/CD40L; P<0.05). Gene ontology analysis revealed several biological networks associated with BKV immune control in comparison to the control group. This study demonstrated that asymptomatic BK viruria is associated with a different intrarenal regulation of several genes implicating in antiviral immune response

Central Disorders of Hypersomnolence: Association with Fatigue, Depression and Sleep Inertia Prevailing in Women

Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p p p p p = 0.0005), and HADS anxiety scale (r = 0.528; p p p p p p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women

Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3-year follow-up period. At our site, 93 Eurodiale-enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes-related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU-related factors [peripheral arterial disease, ulcer infection, C-reactive protein (CRP) and; foot deformities]. During the 3-year follow-up period, a DFU had recurred in 42 patients (575%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 862, 95% confidence interval (CI) 22-332]; presence of osteomyelitis (OR 517, 95% CI 14-187); HbA1c > 75% ([DCCT], OR 407, 95% CI 11-156) and CRP > 5 mg/l (OR 427, 95% CI 12-157). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3-year follow-up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors

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Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices

Difference in Serum Endostatin Levels in Diabetic Patients with Critical Limb Ischemia Treated by Autologous Cell Therapy or Percutaneous Transluminal Angioplasty

The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO 2 ) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO 2 at 1 month after ACT ( r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor

IgA Nephropathy in Czech Patients - Are We Able Reliably Predict the Outcome?

Background/Aims: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. Methods: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. Results: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables [hypertension, sex, GFR, proteinuria, age] was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria Conclusion: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients