Antibody responses to inactivated SARS-CoV-2 vaccine in peritoneal dialysis patients.

INTRODUCTION: As end-stage renal disease (ESRD) patients generally have reduced responses to the vaccines, effectiveness of newly developed SARS-CoV-2 vaccines in ESRD are also matters of curiosity. We aimed to investigate the humoral responses of our peritoneal dialysis (PD) patients to the inactivated SARS-CoV-2 vaccine. METHODS: Humoral immune responses of 23 PD patients who received two doses of the inactivated SARS-CoV-2 vaccine were investigated with a commercial test that measures IgG antibodies towards receptor binding domain of SARS-CoV-2 spike protein. Seropositivity rates, antibody titers, and ESRD related clinical data were compared with 51 hemodialysis (HD) patients and 29 healthy volunteers. RESULTS: Seropositivity of PD patients with the inactivated vaccine was 95.6%. Both the rate of seropositivity and SARS-CoV-2 IgG antibody levels in PD patients were not different from the healthy controls (p = 0.85 and 0.19, respectively). While seropositivity rates were not different for PD or HD patients (p = 0.09), the magnitude of humoral responses was significantly higher in PD patients (p = 0.0001). There were no vaccine-related serious adverse events. In the 3-months clinical follow-up, none of the patients experienced SARS-CoV-2 infection. CONCLUSION: Two doses of the inactivated vaccine generate adequate humoral immune response in PD patients without any serious adverse events.

To what extent can we achieve mineral bone metabolism treatment targets suggested by the KDIGO guidelines among chronic kidney disease stage 3 - 5 non-dialysis patients?

INTRODUCTION: Real-life data on the predialysis management of chronic kidney disease (CKD) is scarce. In this study, our aim was to investigate the current clinical practice and compliance among nephrologists with the KDIGO chronic kidney disease-mineral and bone disorder (CKD-MBD) guidelines. MATERIALS AND METHODS: In this multicenter cross-sectional study, we recruited stage 3 - 5 non-dialysis (ND) CKD patients and recorded the data related to CKD-MBD from two consecutive outpatient clinical visits 3 - 6 months apart. We calculated the therapeutic inertia for hyperphosphatemia, hypocalcemia, hyperparathyroidism, and hypovitaminosis D, in addition to overtreatment for hypophosphatemia, hypercalcemia, hypoparathyroidism, and hypervitaminosis D. RESULTS: We examined a total of 302 patients (male: 48.7%, median age: 67 years). The persistence of low 25-hydroxy vitamin D levels was the most common laboratory abnormality related to CKD-MBD (61.7%), followed by hyperparathyroidism (14.8%), hyperphosphatemia (7.9%), and hypocalcemia (0.0%). According to our results, therapeutic inertia seems to be a more common problem than overtreatment for all the CKD-MBD laboratory parameters that we examined. Therapeutic inertia frequency was highest for hypovitaminosis D (81.1%), followed by hypocalcemia (75.0%), hyperparathyroidism (59.0%), and hyperphosphatemia (30.4%). CONCLUSION: We concluded that CKD-MBD is not optimally managed in CKD stage 3 - 5 ND patients. Clinicians should have an active attitude regarding the correction of MBD even at the earlier stages of CKD.

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli.

BACKGROUND: In experimentally induced puromycine aminonucleoside nephrosis (PAN) animal models, nephrotic syndrome with minimal change disease and focal and segmental sclerosis-like nephritis similar to that in human is demonstrated; however, the real mechanism of PAN is not yet elucidated. Platelet derived endothelial cell growth factor (PD-ECGF), an endothelial mitogen protein, is believed to take part in microvessel formation and in stimulation of angiogenesis and its expression has not been totally demonstrated in PAN rats yet. In this study, we aimed to examine PD-ECGF expression in acute and chronic PAN induced in rats and find out the association between its expression and the stages of angiogenesis in kidney. METHODS: For the experiment, twenty-four Male Wistar Albino rats were used and divided into four groups; control group (n = 6), pre-proteinuria group (n = 6), acute group (n = 6) and chronic group (n = 6). We compared statistically all data by One-way ANOVA Test followed by Dunn Multiple Comparison Test. RESULTS: Proteinurea levels in control and pre-proteinuria groups were not statistically different; however, it was remarkably higher in the acute nephrosis group and significantly greater in the chronic nephrosis group than control group (p < 0.0025). In pre-proteinuria group, the serum albumin and creatinine clearances also did not significantly differ from the control group. On the other hand, in the acute and chronic nephrosis groups, serum albumin and creatinine clearances progressively decreased (p < 0.05). In our immunohistochemical studies, we showed elevated PD-ECGF expression in glomeruli of acute and chronic PAN rats. Microscopic and ultrastructural appearances of the glomeruli of acute and chronic PAN showed various sequential steps of angiogenesis, macrophages and immature capillaries with primitive lumens and apoptotic endothelial cells in the increased mesangial matrix. CONCLUSIONS: It is reported that acute and chronic PAN progressively increase PD-ECGF expression and following induction of angiogenesis in the affected glomeruli.

Waning of SARS-CoV-2 Vaccine-Induced Immune Response over 6 Months in Peritoneal Dialysis Patients and the Role of a Booster Dose in Maintaining Seropositivity.

INTRODUCTION: Although lower than general population, newly developed SARS-CoV-2 vaccines generate immune responses in end-stage kidney disease patients. However, the persistence of immune responses in the long term is not known yet. This study aimed to evaluate humoral immune responses in peritoneal dialysis (PD) patients over 6 months and to analyze the effects of the booster dose. METHODS: Humoral immune responses of PD patients were measured after initial SARS-CoV-2 vaccinations and after 6 months following initial vaccinations. Immune responses were compared between patients who received and did not receive booster doses. PD patients were compared with 41 hemodialysis (HD) patients and 61 healthy controls. Humoral immune responses were measured by a commercial test that detects antibodies toward the receptor-binding domain of the spike protein of SARS-CoV-2. RESULTS: Twenty PD patients were evaluated over 6 months. The initial seropositivity rate was 90.9% with inactivated vaccine and 100% with mRNA vaccine. Seropositivity decreased to 44.4% after 6 months, and a booster dose helped in maintaining the 100% of seropositivity (p = 0.005). Magnitude of humoral response at the 6th month was also higher in patients who received the third dose (1,132.8 ± 769.6 AU/mL vs. 400.0 ± 294.6 AU/mL; p = 0.015). Among patients who did not receive the third dose, those who got mRNA vaccine could maintain higher seropositivity than others who got inactivated vaccine (75% vs. 40% for PD, 81.8% vs. 50% for HD). Seropositivity and antibody levels were similar for PD and HD patients after 6 months (p = 0.24 and 0.56) but lower than healthy controls (p = 0.0013). CONCLUSION: SARS-CoV-2 vaccine-induced antibody levels and seropositivity of PD patients significantly fall after 6 months. A booster dose after around 3 months following initial immunization might help in maintaining seropositivity.

Antibody responses to the SARS-CoV-2 vaccines in hemodialysis patients: Is inactivated vaccine effective?

INTRODUCTION: Vaccines generally have reduced effectiveness in hemodialysis patients and a similar condition may also apply for the SARS-CoV-2 vaccines. The aim of this study was to analyze humoral responses of hemodialysis patients to SARS-CoV-2 vaccines. METHODS: Eighty-five maintenance hemodialysis patients who received either inactivated or mRNA SARS-CoV-2 vaccines were investigated. Antibody levels were measured by a commercial antibody kit, which detected antibodies toward receptor binding domain of the SARS-CoV-2 spike protein. Comparative analyzes were carried between vaccine groups and with a control group of 103 healthy volunteers. RESULTS: Seropositivity rate and antibody levels were significantly lower in hemodialysis patients who received inactivated vaccine (p = 0.000). While mRNA vaccine had better immunogenicity, both vaccines protected from symptomatic infection when seropositivity was achieved. DISCUSSION/CONCLUSION: When used in the same dose with the general population, inactivated SARS-CoV-2 vaccines generate reduced humoral response in hemodialysis patients. mRNA vaccines have better immunogenicity in this group.

Prevalence of anemia in predialysis chronic kidney disease: Is the study center a significant factor?

OBJECTIVES: Anemia is highly prevalent in chronic kidney disease patients; however, its identification and management have been reported to be suboptimal. In this study we aimed to describe the prevalence, severity, risk factors, and treatment of anemia in different nephrology centers, among chronic kidney disease patients who were not given renal replacement therapy. MATERIALS AND METHODS: We performed a multicenter cross-sectional study in three different nephrology clinics. Adult (>18 years of age) chronic kidney disease patients with an estimated glomerular filtration rate (eGFR) below 60 ml/min, and who were not started dialysis were recruited. Demographic, clinical and laboratory data regarding anemia and its management were collected using a standard data form. Anemia was defined as a hemoglobin level below 12g/dL and severe anemia as a hemoglobin level below 10g/dl. RESULTS: A total of 1066 patients were enrolled in the study. Anemia and severe anemia were present in 55.9% and 14.9% of the patients, respectively. The mean hemoglobin level for the whole cohort was 11.8±1.8 g/dL. Univariate analyses revealed that the mean hemoglobin level was significantly different among the centers. Moreover, the frequency of the presence of anemia stratified by severity was also significantly different among the centers. According to binary logistic regression analysis, gender, levels of eGFR and iron, ferritin ≥ 100 ng/mL, and the nephrology center were independent determinants of severe anemia. CONCLUSIONS: We found a high prevalence of anemia among chronic kidney disease patients who were not on renal replacement therapy. Each center should determine the treatment strategy according to the patient's characteristics. According to our results, the center-specific management of anemia seems to be important.

Assessment of DNA oxidation and antioxidant activity in hypertensive patients with chronic kidney disease.

The aim of this study was to evaluate the oxidative DNA damage, antioxidant activity, and effects of antihypertensive drugs on oxidative stress in hypertensive patients with different stages of chronic kidney disease (CKD). Fifty-three non-dialyzed hypertensive CKD patients were included by the study. Serum and urinary 8-hydroxydeoxy guanosine (8-OHdG) levels (as a marker of oxidative DNA damage), serum superoxide dismutase (SOD), and glutathione peroxidase (G-Px) activities (as antioxidant enzymes) were measured. SOD activity was higher and G-Px activity was lower in the patient group as compared to control group. Serum and urinary 8-OHdG levels were found to be higher in the patients with proteinuria greater than 3 g/day than those in the patients with proteinuria less than 3 g/day. It has been determined that G-Px activity and urinary 8-OHdG level were lower in the patients treated with angiotensin-converting enzyme (ACE) inhibitor compared to patients treated with calcium channel blocker. The present data show oxidative DNA damage at a higher level in the patients with proteinuria greater than 3 g/day. In comparison to a calcium channel blocker, an ACE inhibitor seems much more protective against oxidative DNA damage in hypertensive patients with different stages of CKD.

The relationship between glomerular function and podocyte structure of pre-proteinuria and acute nephrosis in puromycin aminonucleoside-induced rat models: a comparative electron microscopic study.

Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.

Ultrasonographic maturation of native arteriovenous fistulae: a follow-up study.

BACKGROUND/AIMS: Ideal time needed for arteriovenous fistula (AVF) maturation is still controversial. In this study, we aimed to investigate the natural course of AVF maturation and also investigated the factors affecting AVF maturation. METHODS: We studied 31 (21M/10F, mean age 55.8 +/- 16.2) chronic renal failure patients. We evaluated the patients with color Doppler ultrasound examination before the fistula operation, at the first day, and at the first, second, third, and sixth months. Radial artery (RA) diameter, flow velocity, flow, resistance index, fistula vein diameter, flow velocity, and flow were measured. RESULTS: Patency rates at the first post-operative day and the sixth month were 87.1% and 67.1%, respectively. Cephalic vein flow was 451.2 +/- 248.6 mL/min at the first month and 528.6 +/- 316.5 mL/min at the sixth month. Baseline RA diameter was lower in failing fistulas than that of patent fistulas. Failing fistulas were more common in women. CONCLUSION: Blood flow was enough for hemodialysis at the end of the first month. However, fistula maturation had continued until the end of the study; women and patients with low RA diameter are particularly prone to fistula failure. Therefore, especially in these patients, AVF must be created at least three or four months before the predicted hemodialysis initiation time.

The effect of renal transplantation on pulmonary function.

In patients with chronic renal failure, mechanical and hemodynamic changes could occur in the lungs without obvious pulmonary symptoms and findings and their effects could pave the way to pulmonary functional disorders. In this study, pulmonary functional disorders and especially alveolocapillary defects, which are frequently seen in uremia, were determined in renal transplanted patients. Pulmonary functions and diffusion capacity were assessed in uremic patients (n = 20) and in successfully transplanted patients (n = 20) without any lung disease or pulmonary edema symptoms and findings. Patients were selected randomly among outpatients who were followed up in a Nephrology and Transplantation Unit. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF25-75) were measured. Single breath carbon monoxide diffusion test and diffusion lung capacity adjusted for hemoglobin concentration (DLAdj) were done. The means of the spirometric values such as FVC, FEV1 and FEV1/FVC were normal in the nondialyzed uremic group, but the PEF25-75 value (68.7%) and diffusion capacity (DLAdj 72.7%) were found to be slightly low. There were 2 patients with normal values and 18 patients with some functional abnormalities in this nondialyzed uremic group. The means of all spirometric parameters and diffusion capacities were found to be normal in the transplanted group. There were 7 patients with normal function and 13 patients with some functional abnormalities in this transplanted group. When the nondialyzed uremic group and the transplanted group were compared statistically, significant differences were found between their spirometric values (except for FVC) and their diffusion capacities. Even though the uremic patients did not show any symptoms, their pulmonary function tests, especially diffusion capacity, were found to be disturbed. Although the transplanted patients as a group had normal mean spirometric values and diffusion capacity there were nevertheless many individual transplanted patients with defective diffusion capacity and abnormal spirometric values.