The importance of paraoxonase 1 activity in chronic kidney disease.

Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.

Placental and Renal Pathways Underlying Pre-Eclampsia.

Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction. Chronic kidney disease is an established risk factor for the development of pre-eclampsia, as angiogenic homeostasis is altered and the maternal circulation is already hypertensive. Facing pre-eclampsia in the context of chronic kidney disease is a challenging emergency for both the mother and the fetus. The clinical features and the management of this multi-organ disorder are clearly defined in the modern literature but the underlying pathophysiologic mechanisms remain not fully elucidated. Understanding the pathophysiology that mediates the onset of pre-eclampsia itself and in synergy with chronic kidney disease is fundamental for developing prompt prevention strategies, treatment planning, and patient counseling. This review aims to summarize the main molecular mechanisms involved in the process of pre-eclampsia, with a particular focus on the role of the kidneys and hormonal pathways related to renal function in normal pregnancy and pre-eclamptic syndromes.

Perceptions of Teamwork and Knowledge Attitudes of Hemodialysis Unit Nurses on Infection Prevention.

INTRODUCTION: The Nurses of Hemodialysis Units: it is necessary to face HAIs (hospital-acquired infections) as a "well-tuned" teamwork. The aim of this study was to investigate the perceptions of the teamwork as well as the knowledge attitudes of the nurses of hemodialysis units on infection prevention in Greece. METHODOLOGY: A cross-sectional survey was conducted with a sample of 1018 HCWs (health care workers) of hemodialysis units in Greece. The questionnaires used were: Teamwork Perceptions Questionnaire (T-TPQ) TeamSTEPPS®-Instructor Manual, and questionnaire APPENDIX A. RESULTS: The majority of them were nurses (69.45%) and nurse assistants (23.87%). About teamwork perceptions per factor, we observed uniformity in their responses with very high rates of agreement. The attitudes of nurses of hemodialysis units on the prevention of infections were distinguished in particularly high rates of compliance with a high perception of the risk of transmission of infections with better compliance being that of women. Also, women seem to be more knowledgeable about diseases that mostly affect the pediatric population. It seemed that level of knowledge between the two sexes did not differ regarding HBV (63.16% vs. 66.71%, p = 0.430), HCV (63.91% vs. 66.71%, p = 0.553), HIV infection (78.95% vs. 81.76%, p = 0.471), and influenza (55.64% vs. 59.61%, p = 0.394). CONCLUSIONS: This study highlighted for the first time the high level of perceptions of teamwork of the HCWs of the hemodialysis units in Greece. It is recommended to investigate the correct application of prevention measures and to detect the causes of deviation from good practices with subsequent investigations on hemodialysis units of Greece.

Anxiety-Depression of Dialysis Patients and Their Caregivers.

Background and Objectives: Anxiety-depression of patients undergoing hemodialysis has a strong relation with the levels of anxiety-depression of their caregivers. The aim of this study was to evaluate anxiety-depression of dialysis patients and their caregivers. Materials and Methods: In this cross-sectional study, 414 pairs of patients and caregivers from 24 hemodialysis centers of Greece completed the Hospital Anxiety and Depression Scale (HADS). The statistical analysis of the data was performed through the Statistical Program SPSS version 20.0. The statistical significance level was set up at 5%. Results: The mean age of patients was 64 (54.06-72.41) years old and the mean duration of hemodialysis was 36 (16-72) months. The mean age of caregivers was 54 (44-66) years old. Of the total sample, 17.1% (n = 71) of patients had high levels of anxiety and 12.3% (n = 51) had high levels of depression. Additionally, 27.8% (n = 115) of caregivers had high levels of anxiety and 11.4% (n = 47) had high levels of depression. Caregivers had higher levels of anxiety when their patients had high levels of anxiety as well (42.3%). Additionally, they had higher levels of depression when their patients had high levels of depression as well (17.6%). Conclusions: The results of this study showed a significant association between the levels of anxiety and depression among patients and caregivers. There is a necessity for individualized assessment of dialysis patients and their caregivers and the implementation of specific interventions for reducing the levels of anxiety and depression among them.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS: We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.

Association of lipid profile with serum PON1 concentration in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk of atherosclerotic events; dyslipoproteinemia and the decrease of the HDL-linked enzyme paraoxonase 1 (PON1), might have a major role. This study intends to compare the association between lipid profile and serum PON1 levels in renal failure (RF) and hemodialysis (HD) patients. Serum lipids, HDL-subclasses and PON1 concentration were evaluated in 90 patients with CKD, divided into groups: RF (n = 46) and HD (n = 44), and in 30 normal individuals (control group). The results showed that PON1 was significantly lower in HD patients than in RF and controls (p < 0.001). In RF patients under statin therapy, PON1 did not differ from that of patients without statins. In HD patients without statins, PON1 was considerably low, whereas in HD with statins (30.42 ± 12.62 µg/mL) was lower than RF with statins (49.31 ± 14.94, p < 0.001). PON1 concentration was significantly and positively associated with HDL-C, HDL3-C and Apo A1 in all groups. Additionally, in HD patients PON1 was negatively associated with LDL-C. Multiple regression analysis revealed that LDL-C and statin treatment were independently related to PON1 concentration in HD patients (ß = -0.331, p = 0.026 and ß = 0.344, p = 0.020, respectively). In RF patients, HDL3-C and Apo A1 are strong determinants of PON1 levels. It is concluded that different parameters of lipid profile seem to affect serum PON1 concentration of RF and HD patients and probably contribute to the delay of atherosclerosis.

Caregivers' experience in patients with chronic diseases.

The aim of this study was to describe the characteristics of caregivers of patients with chronic diseases, assess their perceived burden, and investigate factors influencing this burden. Seventy-three patient-attendants (43 men and 30 women) participated in the pilot-research conducted by two clinics. Of them, 68% attended patients with a malignant disease and 32% attended patients in the end stage of renal disease. Based on questionnaire data, the influence of the social support was studied, in particular that of family members or through state programmers. Family members are the primary caregivers (spouses 51%, children 29%, and others 20%). Psychological support is the main important help that they need and there are a small number of caregivers who have access to a network of medical and social support. It is found that the family still remains the main supporting mechanism for attendants and patients in our population.

Current therapeutic approach of chronic kidney disease-mineral and bone disorder.

Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances.

Investigation of Social Constraints, Psychosocial Adjustment and Optimism among Dialysis Patients.

BACKGROUND: Social constraints are perceived as unsupportive behaviors, leading to inadequate psychosocial adjustment, while optimism can help people recover from distress and reduce any negative effects of chronic disease. The aim of this study was to investigate social constraints, psychosocial adjustment and optimism among patients on dialysis. METHODS: In this study, 402 patients undergoing dialysis in Greece completed the following questionnaires: (i) the Social Constraints Scale (SCS) for the assessment of social constrains, (ii) the Psychosocial adjustment to illness scale (PAIS-SR) for the assessment of psychosocial adjustment, and (iii) the LOT-R scale for the assessment of optimism. A Mann-Whitney test was used for the comparison of continuous variables between two groups. Spearman correlation coefficients (rho) were used to explore the association of two continuous variables. Multiple linear regression analysis was used with the SCS scale. RESULTS: Greater difficulty in psychosocial adjustment in the domestic, vocational, extended family and social environments, sexual relationships, and health care as well as greater psychological distress were significantly associated with a greater occurrence of social constraints (p < 0.001). Additionally, greater optimism was significantly associated with fewer social constraints and lower difficulty in adjusting to their disease (p < 0.001). CONCLUSIONS: Greater difficulty in all dimensions of psychosocial adjustment is associated with more social constraints, while optimism is associated with fewer social constraints and better disease adjustment.

Erythropoietin Effect on Complement Activation in Chronic Kidney Disease.

The complement system is an important part of innate immunity. Despite its known protective role, the complement system may contribute to increased inflammation and tissue injury in cases where its balanced activation is disrupted. The kidneys have been shown to be largely affected by complement dysregulation. The aim of the present study was to investigate the effect of erythropoietin administration, on the complement system, in chronic kidney disease patients. The study involved 20 patients with CKD who received erythropoietin and measurements of levels of complement factors C3a and C5a and complement regulatory proteins (CregPs) CD55, CD46, and CD59. An increase in serum C3a and C5a levels was observed in response to EPO therapy. The increase in C3a was statistically significant (p < 0.05) and concurrent with a statistically significant decrease in CD55 in CD4+ T cells (p < 0.05) and B cells (p < 0.05) and CD59 levels in CD4+ and CD8+ T cells (p < 0.05) at completion of EPO therapy compared with healthy controls. The above observations demonstrate that EPO induces complement activation in patients undergoing EPO therapy with a simultaneous restriction of CRegPs expression, thus possibly allowing the uncontrolled complement activation, which may contribute to tissue injury and disease progression.

Novel biomarkers of acute kidney injury in the general adult ICU: a review.

Acute kidney injury is one of the most frequent problems occurring in the critically ill patients of the intensive care units and it is well established that it increases both morbidity and mortality in these patients. Moreover, despite technological and pharmaceutical advances during the last decades, the incidence as well as the mortality associated with acute kidney injury in these patients remains unchanged. Creatinine, the most common renal dysfunction biomarker in use, has many disadvantages, such as time delay in its increase and the influence by other factors on its serum concentration, such as age, gender, muscle mass, etc. Hence, the need for better renal biomarkers in order to timely intervene for acute kidney injury prevention is imperative. The lack of an early biomarker is an obstacle for the development of new acute kidney injury prevention strategies. With the incidence of acute kidney injury reaching epidemic dimensions, the need for novel markers is urgent. During the last years, the research for finding such biomarkers has been intense. The purpose of the present article is to review the studies which have tested the predictive ability of those markers (in urine and/or plasma) for early detection of acute kidney injury in the mixed adult intensive care unit population and underline the potential limitations encountered in the various studies.

Intensification of peritoneal dialysis improves valacyclovir neurotoxicity.

Valacyclovir induced neurotoxicity is a life-threatening complication, usually starting 24-48 h after drug-peak serum concentrations. The elderly with impaired renal function seem to be the most susceptible group to valacyclovir neurotoxicity. Although hemodialysis is considered the best method for rapid drug removal, our case showed that intensive peritoneal dialysis regimen leads to the recovery of neurotoxicity after 3 days.

Hemolytic-uremic syndrome, malignant hypertension and IgA nephropathy: successful treatment with plasma exchange therapy.

A young patient with hemolytic-uremic syndrome and malignant hypertension with serious deterioration of renal function is described whose biopsy specimen showed additional IgA mesangial deposits. The patient responded to steroid treatment and to plasma exchange therapy without the need of hemodialysis sessions. In the following years, he achieved clinical remission and his blood pressure was in normal ranges without any further complications. IgA glomerulonephritis is rarely associated to hemolytic-uremic syndrome and malignant hypertension, with only a few previously described cases. We present an overview of potential pathophysiological connections between these diseases.

Successful non-surgical treatment of perirenal haematoma after percutaneous renal artery angioplasty in a solitary kidney.

Renal artery angioplasty with stent placement represents an effective choice for correcting renal artery stenosis. However, if iatrogenic renal artery injury occurs, as in the case of solitary kidney, the risk of requiring chronic dialysis increases. This article reports the case of a patient with a solitary kidney, who underwent renal stenting and developed a retroperitoneal haematoma. The patient was managed conservatively and the perirenal haematoma resolved. Within the period of follow-up, the patient had maintained stable renal function with adequate blood pressure control.

Multiple histopathological skin alterations in a hemodialysis patient with severe pruritus.

Pruritus is an alarming symptom in patients with end-stage renal disease (ESRD) accompanied by sleep disturbances and physical and mental disorders. Although its prevalence is very high among hemodialysis patients (90%), its etiology and its successful treatment have been unconfirmed (Melo N, Elias R, Castro M, Romao G, Abensur H. Pruritus in hemodialysis patients: The problem still remains. Hemodial Int. 2009;13:38-42.). Common pruritus etiologies, such as high parathyroid hormone levels, dialysis inadequacy, and iron deficiency are matters of conflict. The case of a hemodialysis patient with consistent itching and a variety of cutaneous eruptions, which after performing skin biopsy were explored and cured, is described. This article addresses the possibility of other causes of pruritus in ESRD and encourages watchful waiting with simple medical interventions, which would relieve patients' symptoms.

Is there any association between IgA nephropathy, Crohn's disease and Helicobacter pylori infection?

A case of IgA nephropathy (IgAN) associated with Crohn's disease (CD) and preceded Helicobacter pylori (Hp) infection is described. Therapy with corticosteroids and azathioprine resulted in clinical improvement. The connection between IgAN and CD is well established, while tonsillar Hp is a potential antigen causative of IgAN. The three entities may reflect a common immunopathogenetic mechanism involving an IgA response to mucosal challenge.

Lipid abnormalities and oxidized LDL in chronic kidney disease patients on hemodialysis and peritoneal dialysis.

Dyslipoproteinemia and oxidative modification of low-density lipoprotein (oxLDL) contribute to the development of oxidative stress and atherosclerosis in chronic kidney disease (CKD). On the contrary, high-density lipoprotein cholesterol (HDL-C), especially HDL3-C subtype, has protective effect against oxidative damage. There is limited evidence referring HDL-C subclass levels in patients on dialysis. This study was designed to compare lipid abnormalities and oxLDL levels in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum lipids, HDL subclasses, and oxLDL were measured in 55 patients with CKD-stage 5 (31 patients on HD and 24 patients on PD) and in 21 normal controls (NC). The results showed that in dialysis patients, triglycerides were higher than in controls (p < 0.0001) and HDL-C was significantly lower (p < 0.0001). The HDL2-C subclass concentration did not differ significantly between patients and controls, while HDL3-C was lower in patients (11 ± 0.5 mg/dL) than in NC (23 ± 1, p < 0.0001). oxLDL levels were markedly increased in patients (1.92 ± 0.29 mg/L) compared to NC (0.22 ± 0.05, p < 0.0001). Patients on PD had higher levels of cholesterol (p < 0.001) and apolipoprotein B (p < 0.05) than patients on HD. However, HDL-C, HDL-C subclasses, and oxLDL concentrations did not differ significantly between PD and HD patients. It is concluded that patients with CKD have a nearly 10-fold elevation of oxLDL compared with NC. Patients on PD have differences in the lipid profile compared with patients on HD; however, both modalities seem to possess similar potential to atherosclerosis development.

Prognostic and Diagnostic Value of Endocan in Kidney Diseases.

Endocan, previously called endothelial cell-specific molecule-1, is a soluble proteoglycan that is predominantly expressed in vascular endothelial cells of the lungs and kidneys. It is upregulated by proinflammatory cytokines and plays a critical role in inflammatory, proliferative, and neovascularization processes. The utility of endocan as a biomarker in a wide spectrum of diseases is being increasingly acknowledged. In this review, we summarize the current evidence concerning the role of endocan in kidney diseases, with emphasis on its prognostic and diagnostic value. It seems that the determination of plasma endocan levels may provide useful prognostic information in many types of renal failure such as chronic kidney disease, IgA nephropathy, and diabetic nephropathy. Endocan could additionally improve the early diagnostic evaluation of acute kidney disease, chronic renal allograft injury, and acute rejection after kidney transplantation, thus contributing to endothelial cell injury monitoring in a timely manner.

The Role of Heme Oxygenase-1 as an Immunomodulator in Kidney Disease.

The protein heme oxygenase (HO)-1 has been implicated in the regulations of multiple immunological processes. It is well known that kidney injury is affected by immune mechanisms and that various kidney-disease forms may be a result of autoimmune disease. The current study describes in detail the role of HO-1 in kidney disease and provides the most recent observations of the effect of HO-1 on immune pathways and responses both in animal models of immune-mediated disease forms and in patient studies.

Association Between Vaccination Status and Mortality Among Intubated Patients With COVID-19-Related Acute Respiratory Distress Syndrome.

Importance: Although vaccination substantially reduces the risk of severe COVID-19, it is yet unknown whether vaccinated patients who develop COVID-19 and require invasive mechanical ventilation have lower mortality than controls. Objective: To examine the association between COVID-19 vaccination status and mortality among critically ill patients who require invasive mechanical ventilation owing to acute respiratory distress syndrome (ARDS) related to COVID-19. Design, Setting, and Participants: This multicenter cohort study was performed between June 7, 2021, and February 1, 2022, among 265 consecutive adult patients with COVID-19 in academic intensive care units who underwent invasive mechanical ventilation owing to ARDS. Exposures: Patients in the full vaccination group had completed the primary COVID-19 vaccination series more than 14 days but less than 5 months prior to intubation. This time threshold was chosen because guidelines from the US Centers for Disease Control and Prevention recommend a booster dose beyond that time. The remaining patients (ie, those who were unvaccinated, partially vaccinated, or fully vaccinated <14 days or >5 months before intubation) comprised the control group. Main Outcomes and Measures: The primary outcome was time from intubation to all-cause intensive care unit mortality. A Cox proportional hazards regression model including vaccination status, age, comorbid conditions, and baseline Sequential Organ Failure Assessment score on the day of intubation was used. Results: A total of 265 intubated patients (170 men [64.2%]; median age, 66.0 years [IQR, 58.0-76.0 years]; 26 [9.8%] in the full vaccination group) were included in the study. A total of 20 patients (76.9%) in the full vaccination group received the BNT162b2 vaccine, and the remaining 6 (23.1%) received the ChAdOx1 nCoV-19 vaccine. Patients in the full vaccination group were older (median age, 72.5 years [IQR, 62.8-80.0 years] vs 66.0 years [IQR, 57.0-75.0 years]) and more likely to have comorbid conditions (24 of 26 [92.3%] vs 160 of 239 [66.9%]), including malignant neoplasm (6 of 26 [23.1%] vs 18 of 239 [7.5%]), than those in the control group. Full vaccination status was significantly associated with lower mortality compared with controls (16 of 26 patients [61.5%] died in the full vaccination group vs 163 of 239 [68.2%] in the control group; hazard ratio, 0.55 [95% CI, 0.32-0.94]; P = .03). Conclusions and Relevance: In this cohort study, full vaccination status was associated with lower mortality compared with controls, which suggests that vaccination might be beneficial even among patients who were intubated owing to COVID-19-related ARDS. These results may inform discussions with families about prognosis.