Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events

Objectives. Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. Methods. We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessedand ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. Results. Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis.Conclusion. Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients

Investigation of base excision repair gene variants in late-onset Alzheimer's disease.

Base excision repair (BER) defects and concomitant oxidative DNA damage accumulation play a role in the etiology and progression of late-onset Alzheimer's disease (LOAD). However, it is not known whether genetic variant(s) of specific BER genes contribute to reduced BER activity in LOAD patients and whether they are associated with risk, development and/or progression of LOAD. Therefore, we performed targeted next generation sequencing for three BER genes, uracil glycosylase (UNG), endonuclease VIII-like DNA glycosylase 1 (NEIL1) and polymerase β (POLβ) including promoter, exonic and intronic regions in peripheral blood samples and postmortem brain tissues (temporal cortex, TC and cerebellum, CE) from LOAD patients, high-pathology control and cognitively normal age-matched controls. In addition, the known LOAD risk factor, APOE was included in this study to test whether any BER gene variants associate with APOE variants, particularly APOE ε4. We show that UNG carry five significant variants (rs1610925, rs2268406, rs80001089, rs1018782 and rs1018783) in blood samples of Turkish LOAD patients compared to age-matched controls and one of them (UNG rs80001089) is also significant in TC from Brazilian LOAD patients (p<0.05). The significant variants present only in CE and TC from LOAD are UNG rs2569987 and POLβ rs1012381950, respectively. There is also significant epistatic relationship (p = 0.0410) between UNG rs80001089 and NEIL1 rs7182283 in TC from LOAD subjects. Our results suggest that significant BER gene variants may be associated with the risk of LOAD in non-APOE ε4 carriers. On the other hand, there are no significant UNG, NEIL1 and POLβ variants that could affect their protein level and function, suggesting that there may be other factors such as post-transcriptional or-translational modifications responsible for the reduced activities and protein levels of these genes in LOAD pathogenesis. Further studies with increased sample size are needed to confirm the relationship between BER variants and LOAD risk

Comparison of geriatric nutritional risk index and creatinine index in short-term mortality prediction in maintenance hemodialysis patients

Background/aim: The aim of this study is to analyze and compare the predictive values of the Geriatric Nutritional Risk Index (GNRI) and Creatinine Index (CI) in the short-term mortality of maintenance hemodialysis patients and to determine their best cut-offs. Material and Methods: A total of 169 adult hemodialysis patients were included in this retrospective, cross-sectional, and single-center study. The demographic, clinical, and laboratory data of the month in which the patients were included in the study were obtained from their medical files and computer records. All-cause death was the primary outcome of the study during a 12-month follow-up alter baseline GNRI and CI calculations. Results: The mean age of the study population was 57 +/- 16 years (49.7% were women, 15% were diabetic). During the one-year observation period, 19 (11.24%) of the cases died (8 CV deaths). The optimal cut-off value for GNRI was determined as 104.2 by ROC analysis [AUC = 0.682 +/- 0.06, (95% CI, 0.549-0.815), p = 0.01]. The low GNRI group had a higher risk for all-cause and CV mortality compared to the higher GNRI group (p = 0.02 for both in log-rank test). The optimal sex-specific cut-off was 12.18 mg/kg/day for men [AUC = 0.723 +/- 0.07, (95% CI, 0.574-0.875), p = 0.03] and was 12.08 mg/kg/day for females [AUC = 0.649 +/- 0.13, (95% CI, 0.384- 0.914), p = 0.01]. Patients with lower sex-specific CI values had higher all-cause and CV mortality (p = 0.001 and p = 0.009 in log-rank test, respectively). In multivariate cox models, both GNRI [HR = 4.904 (% 95 CI, 1.77-13.56), p = 0.002] and sex-specific CI [HR = 5.1 (95% CI, 1.38-18.9), p = 0.01] predicted all-cause mortality. The association of GNRI with CV was lost [HR = 2.6 (CI 95%, 0.54-13.455), p = 0.22], but low CI had a very strong association with CV mortality [HR = 11.48 (CI 95%, 1.25 -104), p = 0.03]. Conclusion: In hemodialysis patients, GNRI and CI have similar powers in predicting all-cause short-term mortality. The association of CI with all-cause death depends on gender. On the other hand, sex-specific CI predicts CV mortality better than GNRI

Infectious Complications of Induction Therapies in Kidney Transplantation.

Background: Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patientand graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidneytransplant recipients who received induction therapy with ATG or basiliximab.Material/Methods: We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation betweenJanuary 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primaryendpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpointswere biopsy-proven rejection episodes, graft loss, loss to follow-up, and death.Results: We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higherin the only ATG group compared to the group without induction treatment (p&lt;0.001). There was no significantdifference in the incidence of BKV nephropathy among groups (p&gt;0.05). The dosage of ATG (OR, 10.685; 95%CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death.Conclusions: This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased riskof CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graftand patient’s survival

Endothelial Function In Patients With Familial Mediterranean Fever-Related Amyloidosis And Association With Cardiovascular Events

Objectives. Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. Methods. We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. Results. Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. Conclusion. Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients

Determinants of mortality in a large group of hemodialysis patients hospitalized for COVID-19

Background: Maintenance hemodialysis (MHD) patients are at increased risk for coronavirus disease 2019 (COVID-19). The aim of this study was to describe clinical, laboratory, and radiologic characteristics and determinants of mortality in a large group of MHD patients hospitalized for COVID-19

Characteristics and outcomes of acute kidney injury in hospitalized COVID-19 patients: A multicenter study by the Turkish society of nephrology

Background Acute kidney injury (AKI) is common in coronavirus disease-2019 (COVID-19) and the severity of AKI is linked to adverse outcomes. In this study, we investigated the factors associated with in-hospital outcomes among hospitalized patients with COVID-19 and AKI. Methods In this multicenter retrospective observational study, we evaluated the characteristics and in-hospital renal and patient outcomes of 578 patients with confirmed COVID-19 and AKI. Data were collected from 34 hospitals in Turkey from March 11 to June 30, 2020. AKI definition and staging were based on the Kidney Disease Improving Global Outcomes criteria. Patients with end-stage kidney disease or with a kidney transplant were excluded. Renal outcomes were identified only in discharged patients. Results The median age of the patients was 69 years, and 60.9% were males. The most frequent comorbid conditions were hypertension (70.5%), diabetes mellitus (43.8%), and chronic kidney disease (CKD) (37.6%). The proportions of AKI stages 1, 2, and 3 were 54.0%, 24.7%, and 21.3%, respectively. 291 patients (50.3%) were admitted to the intensive care unit. Renal improvement was complete in 81.7% and partial in 17.2% of the patients who were discharged. Renal outcomes were worse in patients with AKI stage 3 or baseline CKD. The overall in-hospital mortality in patients with AKI was 38.9%. In-hospital mortality rate was not different in patients with preexisting non-dialysis CKD compared to patients without CKD (34.4 versus 34.0%, p = 0.924). By multivariate Cox regression analysis, age (hazard ratio [HR] [95% confidence interval (95%CI)]: 1.01 [1.0-1.03], p = 0.035], male gender (HR [95%CI]: 1.47 [1.04-2.09], p = 0.029), diabetes mellitus (HR [95%CI]: 1.51 [1.06-2.17], p = 0.022) and cerebrovascular disease (HR [95%CI]: 1.82 [1.08-3.07], p = 0.023), serum lactate dehydrogenase (greater than two-fold increase) (HR [95%CI]: 1.55 [1.05-2.30], p = 0.027) and AKI stage 2 (HR [95%CI]: 1.98 [1.25-3.14], p = 0.003) and stage 3 (HR [95%CI]: 2.25 [1.44-3.51], p = 0.0001) were independent predictors of in-hospital mortality. Conclusions Advanced-stage AKI is associated with extremely high mortality among hospitalized COVID-19 patients. Age, male gender, comorbidities, which are risk factors for mortality in patients with COVID-19 in the general population, are also related to in-hospital mortality in patients with AKI. However, preexisting non-dialysis CKD did not increase in-hospital mortality rate among AKI patients. Renal problems continue in a significant portion of the patients who were discharged

ACUTE KIDNEY INJURY IN HOSPITALIZED COVID-19 PATIENTS: A MULTICENTRE STUDY BY TURKISH SOCIETY OF NEPHROLOGY

BackgroundAcute kidney injury (AKI) is common in coronavirus disease-2019 (COVID-19) and theseverity of AKI is linked to adverse outcomes. In this study, we investigated the factors asso-ciated with in-hospital outcomes among hospitalized patients with COVID-19 and AKI.MethodsIn this multicenter retrospective observational study, we evaluated the characteristics andin-hospital renal and patient outcomes of 578 patients with confirmed COVID-19 and AKI.Data were collected from 34 hospitals in Turkey from March 11 to June 30, 2020. AKI defini-tion and staging were based on the Kidney Disease Improving Global Outcomes criteria.Patients with end-stage kidney disease or with a kidney transplant were excluded. Renaloutcomes were identified only in discharged patients.ResultsThe median age of the patients was 69 years, and 60.9% were males. The most frequentcomorbid conditions were hypertension (70.5%), diabetes mellitus (43.8%), and chronic kid-ney disease (CKD) (37.6%). The proportions of AKI stages 1, 2, and 3 were 54.0%, 24.7%,and 21.3%, respectively. 291 patients (50.3%) were admitted to the intensive care unit.Renal improvement was complete in 81.7% and partial in 17.2% of the patients who weredischarged. Renal outcomes were worse in patients with AKI stage 3 or baseline CKD. Theoverall in-hospital mortality in patients with AKI was 38.9%. In-hospital mortality rate was notdifferent in patients with preexisting non-dialysis CKD compared to patients without CKD(34.4 versus 34.0%, p = 0.924). By multivariate Cox regression analysis, age (hazard ratio[HR] [95% confidence interval (95%CI)]: 1.01 [1.0–1.03], p = 0.035], male gender (HR [95%CI]: 1.47 [1.04–2.09], p = 0.029), diabetes mellitus (HR [95%CI]: 1.51 [1.06–2.17], p =0.022) and cerebrovascular disease (HR [95%CI]: 1.82 [1.08–3.07], p = 0.023), serum lac-tate dehydrogenase (greater than two-fold increase) (HR [95%CI]: 1.55 [1.05–2.30], p =0.027) and AKI stage 2 (HR [95%CI]: 1.98 [1.25–3.14], p = 0.003) and stage 3 (HR [95%CI]:2.25 [1.44–3.51], p = 0.0001) were independent predictors of in-hospital mortality.ConclusionsAdvanced-stage AKI is associated with extremely high mortality among hospitalizedCOVID-19 patients. Age, male gender, comorbidities, which are risk factors for mortality inpatients with COVID-19 in the general population, are also related to in-hospital mortality inpatients with AKI. However, preexisting non-dialysis CKD did not increase in-hospital mor-tality rate among AKI patients. Renal problems continue in a significant portion of thepatients who were discharged.&nbsp;</div