The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials.

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.

Effects of Cinacalcet on Post-transplantation Hypercalcemia and Hyperparathyroidism in Adult Kidney Transplant Patients: A Single-Center Experience.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS:  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. CONCLUSIONS: 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.

Heme oxygenase-1 deficiency as an extremely rare cause of AA-type renal amyloidosis: Expanding the clinical features and review of the literature.

Heme oxygenase-1 (HMOX-1) is an enzyme that regulates heme degradation. Antiinflammatory, antioxidant, and cytoprotective effects of HMOX-1 were also described. It is encoded by the HMOX1 gene, and biallelic mutations cause HMOX-1 deficiency, which is a rare chronic multisystemic inflammatory disorder. This inflammatory status could lead to the development of secondary AA-type amyloidosis theoretically. Here, we report a 30-year-old male with AA-type renal amyloidosis due to a chronic inflammatory condition of unknown origin. Paternal consanguinity and dysmorphic features raised suspicion of a rare genetic disorder. Clinical exome sequencing (CES) confirmed the HMOX-1 deficiency diagnosis related to homozygous missense G139V mutation. To the best of our knowledge, our patient is the eleventh HMOX-1 deficiency case in the literature. Also, HMOX-1 deficiency-related systemic AA-type amyloidosis has not been reported before.

Evaluation of Outcomes of Peritoneal Dialysis Patients in the Post-COVID-19 Period: A National Multicenter Case-Control Study from Turkey.

INTRODUCTION: There are not enough data on the post-CO-VID-19 period for peritoneal dialysis (PD) patients affected from COVID-19. We aimed to compare the clinical and laboratory data of PD patients after COVID-19 with a control PD group. METHODS: This study, supported by the Turkish Society of Nephrology, is a national, multicenter retrospective case-control study involving adult PD patients with confirmed COVID-19, using data collected from April 21, 2021, to June 11, 2021. A control PD group was also formed from each PD unit, from patients with similar characteristics but without COVID-19. Patients in the active period of COVID-19 were not included. Data at the end of the first month and within the first 90 days, as well as other outcomes, including mortality, were investigated. RESULTS: A total of 223 patients (COVID-19 group: 113, control group: 110) from 27 centers were included. The duration of PD in both groups was similar (median [IQR]: 3.0 [1.88-6.0] years and 3.0 [2.0-5.6]), but the patient age in the COVID-19 group was lower than that in the control group (50 [IQR: 40-57] years and 56 [IQR: 46-64] years, p < 0.001). PD characteristics and baseline laboratory data were similar in both groups, except serum albumin and hemoglobin levels on day 28, which were significantly lower in the COVID-19 group. In the COVID-19 group, respiratory symptoms, rehospitalization, lower respiratory tract infection, change in PD modality, UF failure, and hypervolemia were significantly higher on the 28th day. There was no significant difference in laboratory parameters at day 90. Only 1 (0.9%) patient in the COVID-19 group died within 90 days. There was no death in the control group. Respiratory symptoms, malnutrition, and hypervolemia were significantly higher at day 90 in the COVID-19 group. CONCLUSION: Mortality in the first 90 days after COVID-19 in PD patients with COVID-19 was not different from the control PD group. However, some patients continued to experience significant problems, especially respiratory system symptoms, malnutrition, and hypervolemia.

Post-COVID-19 outcomes of non-dialysis dependent chronic kidney disease patients: a national, multicenter, controlled study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has a higher mortality in the presence of chronic kidney disease (CKD). However, there has not been much research in the literature concerning the outcomes of CKD patients in the post-COVID-19 period. We aimed to investigate the outcomes of CKD patients not receiving renal replacement therapy. METHODS: In this multicenter observational study, we included CKD patients with a GFR < 60 ml/min/1.73 m2 who survived after confirmed COVID-19. Patients with CKD whose kidney disease was due to diabetic nephropathy, polycystic kidney disease and glomerulonephritis were not included in this study. CKD patients with similar characteristics, who did not have COVID-19 were included as the control group. RESULTS: There were 173 patients in the COVID-19 group and 207 patients in the control group. Most patients (72.8%) were treated as inpatient in the COVID-19 group (intensive care unit hospitalization: 16.7%, acute kidney injury: 54.8%, needing dialysis: 7.9%). While there was no significant difference between the baseline creatinine values of the COVID-19 group and the control group (1.86 and 1.9, p = 0.978, respectively), on the 1st month, creatinine values were significantly higher in the COVID-19 group (2.09 and 1.8, respectively, p = 0.028). Respiratory system symptoms were more common in COVID-19 patients compared to the control group in the 1st month and 3rd month follow-ups (p < 0.001). Mortality at 3 months after the diagnosis of COVID-19 was significantly higher in the COVID-19 group than in the control group (respectively; 5.2% and 1.4%, p:0.037). Similarly, the rate of patients requiring dialysis for COVID-19 was significantly higher than the control group (respectively; 8.1% and 3.4%, p: 0.045). CONCLUSIONS: In CKD patients, COVID-19 was associated with increased mortality, as well as more deterioration in kidney function and higher need for dialysis in the post-COVID-19 period. These patients also had higher rate of ongoing respiratory symptoms after COVID-19.

Characteristics and Survival Results of Peritoneal Dialysis Patients Suffering from COVID-19 in Turkey: A Multicenter National Study.

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.

Middle-term outcomes in renal transplant recipients with COVID-19: a national, multicenter, controlled study.

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

Peripheral innate and adaptive immune cells during COVID-19: Functional neutrophils, pro-inflammatory monocytes, and half-dead lymphocytes.

BACKGROUND: A better understanding of innate and adaptive cells in COVID-19 is necessary for the development of effective treatment methods and vaccines. METHODS: We studied phenotypic features of innate and adaptive immune cells, oxidative burst, phagocytosis, and apoptosis. One hundred and three patients with COVID-19 were grouped according to their clinical features into the categories of mild (35%), moderate (40.8%), and severe (24.3%). RESULTS: Monocytes were CD16+ pro-inflammatory monocytes and tended to shed their HLA-DR, especially in severe cases (p < 0.01). Neutrophils were mature and functional, although a decline of their CD10 and CD16 was observed (p < 0.01). No defect was found in the reactive oxygen species production and their apoptosis. The percentage of natural killer cells was in the normal range, whereas the percentages of CD8+ NK and CD56+ T lymphocytes were found to be high (p < 0.01). Although the absolute numbers of all lymphocyte subsets were low and showed a tendency for a gradual decrease in accordance with the disease progression, the most decreased absolute number was that of B lymphocytes, followed by CD4+ T cells in the severe cases. The percentages of double-negative T cells; HLA-DR+ CD3+ and CD28- CD8+ subsets were found to be significantly increased. Importantly, we demonstrated the increased baseline activation of caspase-3 and increased lymphocyte apoptosis. CONCLUSION: We suggest that SARS-CoV-2 primarily affects the lymphocytes and not the innate cells. The increased baseline activation of Caspase-3 could make the COVID-19 lymphocytes more vulnerable to cell death. Therefore, this may interrupt the crosstalk between the adaptive and innate immune systems.

Immunological parameters associated with the severity of COVID-19 pneumonia in kidney transplant recipients.

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: SO2 > 90%) and severe disease groups (SO2 ≤ 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 SO2 (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.

Characteristics and outcomes of hospitalised older patients with chronic kidney disease and COVID-19: A multicenter nationwide controlled study.

OBJECTIVE: Older adults with co-morbidities have been reported to be at higher risk for adverse outcomes of coronavirus disease 2019 (COVID-19). The characteristics of COVID-19 in older patients and its clinical outcomes in different kidney disease groups are not well known. METHODS: Data were retrieved from a national multicentric database supported by Turkish Society of Nephrology, which consists of retrospectively collected data between 17 April 2020 and 31 December 2020. Hospitalised patients aged 18 years or older with confirmed COVID-19 diagnosis suffering from stage 3-5 chronic kidney disease (CKD) or on maintenance haemodialysis (HD) treatment were included in the database. Non-uraemic hospitalised patients with COVID-19 were also included as the control group. RESULTS: We included 879 patients [388 (44.1%) female, median age: 63 (IQR: 50-73) years]. The percentage of older patients in the CKD group was 68.8% (n = 188/273), in the HD group was 49.0% (n = 150/306) and in the control group was 30.4% (n = 70/300). Co-morbidities were higher in the CKD and HD groups. The rate of presentation with severe-critical disease was higher in the older CKD and HD groups (43.6%, 55.3% and 16.1%, respectively). Among older patients, the intensive care unit (ICU) admission rate was significantly higher in the CKD and HD groups than in the control group (38.8%, 37.3% and 15.7%, respectively). In-hospital mortality or death and/or ICU admission rates in the older group were significantly higher in the CKD (29.3% and 39.4%) and HD groups (26.7% and 30.1%) compared with the control group (8.6% and 17.1%). In the multivariate analysis, in-hospital mortality rates in CKD and HD groups were higher than control group [hazard ratio (HR): 4.33 (95% confidence interval [CI]: 1.53-12.26) and HR: 3.09 (95% CI: 1.04-9.17), respectively]. CONCLUSION: Among older COVID-19 patients, in-hospital mortality is significantly higher in those with stage 3-5 CKD and on maintenance HD than older patients without CKD regardless of demographic characteristics, co-morbidities, clinical and laboratory data on admission.

Predicting the outcome of COVID-19 infection in kidney transplant recipients.

BACKGROUND: We aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of hospital-acquired acute kidney injury on Covid-19 outcomes in patients with and without chronic kidney disease: a multicenter retrospective cohort study

Background/aim: Hospital-acquired acute kidney injury (HA-AKI) may commonly develop in Covid-19 patients and is expected to have higher mortality. There is little comparative data investigating the effect of HA-AKI on mortality of chronic kidney disease (CKD) patients and a control group of general population suffering from Covid-19. Materials and methods: HA-AKI development was assessed in a group of stage 3­5 CKD patients and control group without CKD among adult patients hospitalized for Covid-19. The role of AKI development on the outcome (in-hospital mortality and admission to the intensive care unit [ICU]) of patients with and without CKD was compared. Results: Among 621 hospitalized patients (age 60 [IQR: 47­73]), women: 44.1%), AKI developed in 32.5% of the patients, as stage 1 in 84.2%, stage 2 in 8.4%, and stage 3 in 7.4%. AKI developed in 48.0 % of CKD patients, whereas it developed in 17.6% of patients without CKD. CKD patients with HA-AKI had the highest mortality rate of 41.1% compared to 14.3% of patients with HA-AKI but no CKD (p < 0.001). However, patients with AKI+non-CKD had similar rates of ICU admission, mechanical ventilation, and death rate to patients with CKD without AKI. Adjusted mortality risks of the AKI+non-CKD group (HR: 9.0, 95% CI: 1.9­44.2) and AKI+CKD group (HR: 7.9, 95% CI: 1.9­33.3) were significantly higher than that of the non-AKI+non-CKD group. Conclusion: AKI frequently develops in hospitalized patients due to Covid-19 and is associated with high mortality. HA-AKI has worse outcomes whether it develops in patients with or without CKD, but the worst outcome was seen in AKI+CKD 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. METHODS: 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. RESULTS: 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 × 103 per mm3 versus 192 × 103 per mm3, p = 0.011) and lymphocyte (800 per mm3 versus 1000 per mm3, 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 × 103 per mm3) during hospitalization (HR; 1.864 [95% CI, 1.025-3.390], p = 0.041) were risk factors for mortality. CONCLUSION: 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.

Volume status and arterial blood pressures are associated with arterial stiffness in hemodialysis patients.

BACKGROUND: Arterial stiffness is a strong predictor of mortality in hemodialysis patients. In this study, we aimed to investigate possible relations of arterial stiffness with volume status determined by bioimpedance analysis and aortic blood pressure parameters. Also, effects of a single hemodialysis session on these parameters were studied. METHODS: A total of 75 hemodialysis patients (M/F: 43/32; mean age: 53 ± 17) were enrolled. Carotid-femoral pulse wave velocity, augmentation index, and aortic pulse pressure were measured by applanation tonometry before and after hemodialysis. Extracellular fluid and total body fluid volumes were determined by bioimpedance analysis. RESULTS: Carotid-femoral pulse wave velocity (9.30 ± 3.30 vs 7.59 ± 2.66 m/s, p < 0.001), augmentation index (24.52 ± 9.42 vs 20.28 ± 10.19, p < 0.001), and aortic pulse pressure (38 ± 14 vs 29 ± 8 mmHg, p < 0.001) significantly decreased after hemodialysis. Pre-dialysis carotid-femoral pulse wave velocity was associated with age (r2 = 0.15, p = 0.01), total cholesterol (r2 = 0.06, p = 0.02), peripheral mean blood pressure (r2 = 0.10, p = 0.005), aortic-mean blood pressure (r2 = 0.06, p = 0.02), aortic pulse pressure (r2 = 0.14, p = 0.001), and extracellular fluid/total body fluid (r2 = 0.30, p < 0.0001). Pre-dialysis augmentation index was associated with total cholesterol (r2 = 0.06, p = 0,02), aortic-mean blood pressure (r2 = 0.16, p < 0.001), and aortic pulse pressure (r2 = 0.22, p < 0.001). Δcarotid-femoral pulse wave velocity was associated with Δaortic-mean blood pressure (r2 = 0.06, p = 0.02) and inversely correlated with baseline carotid-femoral pulse wave velocity (r2 = 0.29, p < 0.001). Pre-dialysis Δaugmentation index was significantly associated with Δaortic-mean blood pressure (r2 = 0.09, p = 0.009) and Δaortic pulse pressure (r2 = 0.06, p = 0.03) and inversely associated with baseline augmentation index (r2 = 0.14, p = 0.001). In multiple linear regression analysis (adjusted R2 = 0.46, p < 0.001) to determine the factors predicting Log carotid-femoral pulse wave velocity, extracellular fluid/total body fluid and peripheral mean blood pressure significantly predicted Log carotid-femoral pulse wave velocity (p = 0.001 and p = 0.006, respectively). CONCLUSION: Carotid-femoral pulse wave velocity, augmentation index, and aortic pulse pressure significantly decreased after hemodialysis. Arterial stiffness was associated with both peripheral and aortic blood pressure. Furthermore, reduction in arterial stiffness parameters was related to reduction in aortic blood pressure. Pre-dialysis carotid-femoral pulse wave velocity was associated with volume status determined by bioimpedance analysis. Volume control may improve not only the aortic blood pressure measurements but also arterial stiffness in hemodialysis patients.

Endothelial Progenitor Cells and Kidney Diseases.

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.

CD133+ cells are associated with ADIPOCYTOKINES and endothelial dysfunction in hemodialysis patients.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

A Rare Clinical Entity: Staphylococcus-Related Glomerulonephritis.

Staphylococcus aureus is a rare cause of postinfectious glomerulonephritis, and Staphylococcus-related glomerulonephritis primarily occurs in middle-aged or elderly patients. Patients with Staphylococcus-related glomerulonephritis also present with hematuria, proteinuria of varying degrees, rising serum creatinine levels, and/or edema. The severity of renal insufficiency is proportional to the degree of proliferation and crescent formation. Here, we present a diabetic patient admitted with a history of 1 week of left elbow pain. Laboratory results revealed that erythrocyte sedimentation rate was 110 mm/hour, serum creatinine level was 1 mg/dL, C-reactive protein level was 150 mg/L, and magnetic resonance imaging showed signal changes in favor of osteomyelitis at the olecranon level, with diffuse edematous appearance in the elbow skin tissue and increased intra-articular effusion. After diagnosis of osteomyelitis, ampicillin/sulbactam and teicoplanin were administered. After day 7 of admission, the patient developed acute kidney injury requiring hemodialysis under antibiotic treatment. Kidney biopsy was performed to determine the underlying cause, which showed Staphylococcus-related glomerulonephritis. Recovery of renal functions was observed after antibiotic and supportive treatment.

Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anemia in Predialysis Patients.

BACKGROUND: We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatment. STUDY DESIGN: Single arm, open label study. METHODS: A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 µg/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks). RESULTS: Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE. CONCLUSION: Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs.

Cardiovascular-renal changes after kidney donation: one-year follow-up study.

BACKGROUND: Long-term consequences of kidney donation are not well known. Most of the studies published were focused on renal risk. In this prospective study, we investigated the changes in cardiovascular function after kidney donation. METHODS: Thirty-eight living kidney donors were included. In addition to 24-hr ambulatory blood pressure monitoring, serum interleukin-6, vascular cell adhesion molecule (VCAM), and asymmetric dimethylarginine levels were measured. Endothelial function was examined by measuring ischemia-induced flow-mediated dilation (FMD) of the brachial artery. All studies were repeated at 3 months and 12 months after kidney donation. RESULTS: The mean serum interleukin-6 levels, both at 3 months and 12 months, were significantly increased as compared to the baseline (P = 0.007 and P < 0.001, respectively). The mean serum asymmetric dimethyl-arginine (P < 0.001) and VCAM levels (P < 0.001) at 12 months were significantly increased as compared to baseline. FMD values at 1 year (9.3% ± 7.1%) were significantly decreased as compared to 3 months (13.0% ± 6.0%, P = 0.001) and baseline (13.9% ± 6.3%, P = 0.002). In multivariate analysis, serum uric acid (P = 0.001), estimated glomerular filtration rate (P = 0.027), and VCAM (P = 0.014) levels were the independent predictors of FMD 12 months after kidney donation. CONCLUSION: Our findings suggest that kidney donation might increase the cardiovascular risk in kidney donors.