Hepatitis C virus(HCV)infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies.Patients with HCV infection were found to have ...a higher risk of end-stage renal disease.HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation.Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis(MPGN),membranous nephropathy,focal segmental glomerulosclerosis,fibrillary glomerulonephritis,immunotactoid glomerulopathy,IgA nephropathy,renal thrombotic microangiopathy,vasculitic renal involvement and interstitial nephritis.The most common type of HCV associated glomerulopathy is typeⅠMPGN associated with typeⅡmixed cryoglobulinemia.Clinically,typical renal manifestations in HCV-infected patients include proteinuria,microscopic hematuria,hypertension,acute nephritis and nephrotic syndrome.Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease:(1)antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes;(2)B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins;and(3)nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis.In patients with moderate proteinuria and stable renal functions,anti-HCV therapy is advised to be started as pegylated interferon-αplus ribavirin.However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations,immunosuppressive therapy with cyclophosphamide,rituximab,steroid pulses and plasmapheresis should be administrated.
Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may ...be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs.
Secondary hyperparathyroidism may manifest as hypercalcemia in the post-transplant period. The classical treatment method is parathyroidectomy and the alternative is oral cinacalcet, a calcimimetic ...agent therapy. We retrospectively investigated the effect of cinacalcet therapy on kidney and patient survival in these patients.
In our single-center, retrospective, observational study, files of 934 patients who underwent renal transplantation in our unit between 2008 and 2022 were reviewed. A total of 23 patients were started on cinacalcet for the treatment of hypercalcemia (calcium > 10.3 mg/dl) and parathyroid hormone (PTH) elevation (>65 pg/ml). Patients with calcium < 10.3 mg/dl and PTH > 700 pg/ml at any time in the follow-up after renal transplantation were included in the study. In addition, the demographic data of the patients, baseline creatine, calcium, phosphorus, and PTH levels at the time of hypercalcemia, parathyroid ultrasonography, parathyroid scintigraphy, creatinine, calcium, phosphorus, and PTH levels in the last controls, and survival status were evaluated.
The mean age of 23 patients included in the study was 52.7 ± 11 years (minimum: 32; maximum: 66). Of the patients, 16 (69.6%) were male, and 15 (65.2%) were transplanted from a living donor. Parathyroid scintigraphic revealed adenoma in three (13%) patients, hyperplasia in five patients (21.7%), and no involvement in 15 patients (65.2%). Cinacalcet treatment was initiated at a median of 33 months (interquartile range (IQR) = 13-96) after the kidney transplant operation. There was no graft loss in the patients during the follow-up period. Twenty-two patients (95.7%) were alive, and one patient died. The calcium level of the patients decreased from 11.3 ± 0.64 mg/dl to 9.98 ± 0.78 mg/dl (p = 0.001) after cinacalcet treatment. Phosphorus values increased from 2.7 ± 0.65 mg/dl to 3.10 ± 0.65 mg/dl (p = 0.004). On the other hand, there was no significant difference in PTH levels between the initial and final controls (285 (IQR = 150-573) vs. 260 pg/ml (IQR = 175-411), p = 0.650). Also, creatinine levels were similar (1.2 ± 0.38 vs. 1.24 ± 0.48 mg/dl, p = 0.43). Despite cinacalcet treatment, calcium levels did not decrease in eight patients. Complications such as renal dysfunction and pathological fracture did not develop in these patients.
It seems that cinacalcet treatment is a suitable option for patients with hypercalcemia and/or hyperparathyroidism with low drug interactions and good biochemical control after renal transplantation.
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.
This multicenter, retrospective, observational study collected data from 47 nephrology clinics in Turkey. Baseline clinical, laboratory and radiological characteristics, and COVID-19 treatments during hospitalization, need for intensive care and mechanical ventilation were recorded. The main study outcome was in-hospital mortality and the determinants were analyzed by Cox regression survival analysis.
Of 567 MHD patients, 93 (16.3%) patients died, 134 (23.6%) patients admitted to intensive care unit (ICU) and 91 of the ones in ICU (67.9%) needed mechanical ventilation. Patients who died were older (median age, 66 57-74 vs. 63 52-71 years, p = 0.019), had more congestive heart failure (34.9% versus 20.7%, p = 0.004) and chronic obstructive pulmonary disease (23.6% versus 12.7%, p = 0.008) compared to the discharged patients. Most patients (89.6%) had radiological manifestations compatible with COVID-19 pulmonary involvement. Median platelet (166 × 10
per mm
versus 192 × 10
per mm
, p = 0.011) and lymphocyte (800 per mm
versus 1000 per mm
, p < 0.001) counts and albumin levels (median, 3.2 g/dl versus 3.5 g/dl, p = 0.001) on admission were lower in patients who died. Age (HR: 1.022 95% CI, 1.003-1.041, p = 0.025), severe-critical disease clinical presentation at the time of diagnosis (HR: 6.223 95% CI, 2.168-17.863, p < 0.001), presence of congestive heart failure (HR: 2.247 95% CI, 1.228-4.111, p = 0.009), ferritin levels on admission (HR; 1.057 95% CI, 1.006-1.111, p = 0.028), elevation of aspartate aminotransferase (AST) (HR; 3.909 95% CI, 2.143-7.132, p < 0.001) and low platelet count (< 150 × 10
per mm
) during hospitalization (HR; 1.864 95% CI, 1.025-3.390, p = 0.041) were risk factors for mortality.
Hospitalized MHD patients with COVID-19 had a high mortality rate. Older age, presence of heart failure, clinical severity of the disease at presentation, ferritin level on admission, decrease in platelet count and increase in AST level during hospitalization may be used to predict the mortality risk of these patients.
Purpose
An outbreak of a novel respiratory disease due to coronavirus species was emerged in 2019 and named as Coronavirus Disease-2019 (COVID-19). Clinical and immunological factors affecting the ...course of COVID-19 in kidney transplant recipients (KTR) are not well-known.
Methods
In this prospective observational study, we presented 20 KTR with COVID-19 pnemonia and examined the factors predicting the severity of COVID-19. A total of 10 KTR without COVID-19 was used as control group. Lymphocyte subsets were determined by flow cytometry. In 13/20 patients, immunophenotyping was repeated 1 week later.
Results
Mean age of the patients was 50 ± 9 years. Patients were classified as mild–moderate (oxygen saturation: SO
2
> 90%) and severe disease groups (SO
2
≤ 90%). Serum albumin and hemoglobin were lower and CRP, fibrinogen and peak
d
-dimer were higher in severe group. Peak CRP was inversely associated with nadir SO
2
(
r
= − 0.68,
p
= 0.001). Neutrophil/lymphocyte ratio was higher in severe group (
p
= 0.01). CD3 + and CD4 + cells were lower and NK cell percentage (CD16 + 56 +) was higher in severe group. Percentage of spontaneously activated CD8 cells (CD8 + CD69 +) was higher in severe group. In comparison of KTR with and without COVID-19, CD8 + cells were lower but NK cell percentage was higher in KTR with COVID-19.
Conclusion
In this pilot study, increased NK cells, activated CD8 + cells and decreased CD3 + and CD4 + cells were associated with severity of COVID-19 in KTR. Peripheral immunophenotyping of lymphocyte subtypes may provide prognostic information about the clinical course of COVID-19 in KTR.
We aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19.
We conducted a multicenter, retrospective ...study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission.
One hundred nine patients (male/female: 63/46, mean age: 48.4 ± 12.4 years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60 years) (38.1% vs 14.9%, p = 0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60 years) (39.1% vs. 13.9%; p = 0.004), and had lower serum albumin (3.4 g/dl 2.9-3.8 vs. 3.8 g/dl 3.5-4.1, p = 0.002), higher serum ferritin (679 μg/L 184-2260 vs. 331 μg/L 128-839, p = 0.048), and lower lymphocyte counts (700/μl 460-950 vs. 860 /μl 545-1385, p = 0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60 years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis.
Over the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.
Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, ...receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.
Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.
Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 0.15-0.46 versus 0.18 0.12-0.28, P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.
Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.
This scoping review prepared by endocrinology and nephrology experts aimed to address the significance of finerenone, as a novel therapeutic option, in diabetic kidney disease (DKD), based on the ...biological prospect of cardiorenal benefit due to non-steroidal mineralocorticoid receptor antagonist (MRA) properties, and the recent evidence from the finerenone phase 3 program clinical trials. The importance of finerenone in slowing DKD progression was critically reviewed in relation to the role of MR overactivation in the pathogenesis of cardiorenal disease and unmet needs in the current practice patterns. The efficacy and safety outcomes of finerenone phase III study program including FIDELIO-DKD, FIGARO-DKD and FIDELITY were presented. Specifically, perspectives on inclusion of patients with preserved estimated glomerular filtration rate (eGFR) or high albuminuria, concomitant use of sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide 1 receptor agonist (GLP-1 RA), baseline glycated hemoglobin (HbA1c) level and insulin treatment, clinically meaningful heart failure outcomes and treatment-induced hyperkalemia were addressed. Finerenone has emerged as a new therapeutic agent that slows DKD progression, reduces albuminuria and risk of cardiovascular complications, regardless of the baseline HbA1c levels and concomitant treatments (SGLT2i, GLP-1 RA, or insulin) and with a favorable benefit-risk profile. The evolving data on the benefit of SGLT2is and non-steroidal MRAs in slowing or reducing cardiorenal risk seem to provide the opportunity to use these pillars of therapy in the management of DKD, after a long-period of treatment scarcity in this field. Along with recognition of the albuminuria as a powerful marker to detect those patients at high risk of cardiorenal disease, these important developments would likely to impact standard-of-care options in the setting of DKD.
Introduction: We aimed to study the characteristics of peritoneal dialysis (PD) patients with coronavirus disease-19 (COVID-19), determine the short-term mortality and other medical complications, ...and delineate the factors associated with COVID-19 outcome. Methods: In this multicenter national study, we included PD patients with confirmed COVID-19 from 27 centers. The baseline demographic, clinical, laboratory, and radiological data and outcomes at the end of the first month were recorded. Results: We enrolled 142 COVID-19 patients (median age: 52 years). 58.2% of patients had mild disease at diagnosis. Lung involvement was detected in 60.8% of patients. Eighty-three (58.4%) patients were hospitalized, 31 (21.8%) patients were admitted to intensive care unit and 24 needed mechanical ventilation. Fifteen (10.5%) patients were switched to hemodialysis and hemodiafiltration was performed for four (2.8%) patients. Persisting pulmonary symptoms (n = 27), lower respiratory system infection (n = 12), rehospitalization for any reason (n = 24), malnutrition (n = 6), hypervolemia (n = 13), peritonitis (n = 7), ultrafiltration failure (n = 7), and in PD modality change (n = 8) were reported in survivors. Twenty-six patients (18.31%) died in the first month of diagnosis. The non-survivor group was older, comorbidities were more prevalent. Fever, dyspnea, cough, serious-vital disease at presentation, bilateral pulmonary involvement, and pleural effusion were more frequent among non-survivors. Age (OR: 1.102; 95% CI: 1.032–1.117; p: 0.004), moderate-severe clinical disease at presentation (OR: 26.825; 95% CI: 4.578–157.172; p < 0.001), and baseline CRP (OR: 1.008; 95% CI; 1,000–1.016; p: 0.040) were associated with first-month mortality in multivariate analysis. Discussion/Conclusions: Early mortality rate and medical complications are quite high in PD patients with COVID-19. Age, clinical severity of COVID-19, and baseline CRP level are the independent parameters associated with mortality.
Hemodialysis (HD) patients have increased risk of cardiovascular disease (CVD). Impaired stem cell health and adipocytokine metabolism may play important roles in the complex pathophysiological ...mechanisms of CVD in this patient population. We aimed to investigate the relationships between CD133+ cell counts, adipocytokines and parameters of endothelial dysfunction and atherosclerosis in HD patients.
In 58 chronic HD patients (male/female:28/30, mean age:58 ± 14 years), serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and resistin were measured by ELISA. Left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery were measured. CD133+ cells were counted by flow cytometry (BD FACSCalibur-BD Bioscience,CA).
CD133+ cell counts were inversely associated with FMD (r = -0.39, p = 0.007) and positively correlated with serum resistin (r = 0.45, p < 0.001) and serum TNF-α (r = 0.31, p = 0.02). Serum leptin levels were higher in high CD133 group compared to low CD133 group 32.37(12.74-72.29) vs 15.50(5.38-37.12)ng/mL, p = 0.03. Serum leptin levels were correlated with TNF-α(r = 0.35, p = 0.009). Serum adiponectin levels were negatively correlated with serum leptin (r = -0.28, p = 0.03). Serum resistin levels were associated with TNF-α (r = 0.54, p < 0.001) and leptin (r = 0.29, p = 0.03). Serum IL-6 levels were significantly associated with LVMI (r = 0.31, p = 0.03). Serum IL-6 levels were significantly higher in patients with carotid plaque compared to patients without plaque 12.75(9.91-28.68) vs 8.27(5.97-14.04) pg/mL, p = 0.02. In multiple linear regression analysis to determine the factors predicting LogFMD; dialysis vintage, LVMI and LogCD133+ cell counts were included as independent variables(R = 0.57, adjusted R-square = 0.27, p = 0.001). CD133+ cell count and LVMI were found to significantly predict FMD (p = 0.03 and p = 0.04 respectively).
CD133+ cells were associated with inflammation and endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-α levels were positively related to CD133+ cell count. Impaired regulation of undifferentiated stem cells and adipocytokines might contribute to endothelial dysfunction in HD patients.
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