Neutrophil reactive oxygen formation, bacterial infections and mortality in malnourished hemodialysis patients: Evaluation of clinical outcomes.

INTRODUCTION: Patients with end stage kidney disease undergoing maintenance hemodialysis (MHD) are prone to malnutrition and infections. OBJECTIVE: The objective of this study was to evaluate the effect of polymorphonuclear (PMN) cell dysfunction on clinical outcomes of MHD patients, in association with nutritional status. METHODS: This prospective study investigated 39 MHD patients by evaluating the oxidative activity of their PMN cells using Phorbol 12-Myristate-13-Acetate (PMA) stimulation. Blood samples were taken from each participant at dialysis initiation. Demographics, laboratory data, and clinical outcomes during a 24-month follow-up period were obtained from electronic medical records. RESULTS: Phagocytic activity was described in percentiles of mean fluorescence intensity (MFI) of PMA levels. There were no differences in comorbidities between patients with low or high MFI-PMA percentiles. Patients in the lowest (25th) MFI-PMA percentile (N = 10) had poorer nutritional status and more frequent severe infections compared to the other 29 patients (4.3 ± 3.4 events versus 2 ± 2.2 events, p = 0.017). Furthermore, they had more frequent hospitalizations (>3) due to infections (70% versus 41%, p = 0.073) and their mortality rate was higher (80% versus 31%, p = 0.007). The odds ratio for all-cause mortality was 8.85. In multivariate analysis, the MFI-PMA percentile and ischemic heart disease were the strongest predictors of all-cause mortality (p = 0.02 and p = 0.005, respectively). CONCLUSIONS: Low MFI-PMA levels were associated with poor nutritional status and adverse clinical outcomes and might serve as a prognostic biomarker, predicting severe infections and mortality among malnourished MHD patients.

Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Acute Kidney Injury and Rehabilitation Outcomes among Elderly Patients with Chronic Kidney Disease.

INTRODUCTION: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. METHODS: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. RESULTS: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6-6.5; p = 0.001). CONCLUSION: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI.

Intra-Cranial Arterial Calcifications in Hemodialysis Patients.

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

The Clinical Significance of LDL-Cholesterol on the Outcomes of Hemodialysis Patients with Acute Coronary Syndrome.

Background and objectives: Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods: This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015-2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. Risk factors for 30-day and 1-year mortality were assessed. Results: Among 349 patients included in the analysis, 246 were HD-dependent ("HD group"). HD group patients had higher prevalence of diabetes, hypertension, and heart disease than the control group. At ACS hospitalization, lipid profile and chronic statin treatment were comparable between groups. Odds ratios for 30-day mortality in HD vs. control group was 5.2 (95% CI 1.8-15; p = 0.002) and for 1-year, 3.4 (95% CI 1.9-6.1; p <0.001). LDL and LDL < 70 did not change 30-day and 1-year mortality rates in the HD group (p = 0.995, 0.823, respectively). However, survival after ACS in HD patients correlated positively with nutritional parameters such as serum albumin (r = 0.368, p < 0.001) and total cholesterol (r = 0.185, p < 0.001), and inversely with the inflammatory markers C-reactive protein (CRP; r = -0.348, p < 0.001) and neutrophils-to-lymphocytes ratio (NLR; r = -0.181, p = 0.019). Multivariate analysis demonstrated that heart failure was the only significant predictor of 1-year mortality (OR 2.8, p = 0.002). LDL < 70 mg/dL at ACS hospitalization did not predict 1-year mortality in the HD group. Conclusions: Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition-inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients.

Humoral Response to Pfizer BNT162b2 Vaccine Booster in Maintenance Hemodialysis Patients.

INTRODUCTION: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine. METHODS: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose. RESULTS: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response. CONCLUSIONS: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule.

Humoral Response and SARS-CoV-2 Infection Risk following the Third and Fourth Doses of the BNT162b2 Vaccine in Dialysis Patients.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19.

INTRODUCTION: While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking. METHODS: This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization. RESULTS: Among 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001). CONCLUSION: Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

Presence of galectin-3 in peritoneal dialysate. Does it have a role in the peritoneal membrane inflammatory process?

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin-3 (Gal-3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal-3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin-6 (IL-6) levels was analysed. Gal-3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL-6 levels (0.674, p = 0.002), but not with serum Gal-3 levels or dialysis vintage. Patients who were high transporters had higher Gal-3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL-6 level was the strongest predictor of dialysate Gal-3 levels. This study found Gal-3 in dialysate effluent correlated with D/P creatinine and dialysate IL-6 levels. These findings may imply that Gal-3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further.

The efficacy of rehabilitation for elderly chronic kidney disease patients: a retrospective, single-center study.

BACKGROUND: As the geriatric population is growing rapidly, so is the prevalence of chronic kidney disease (CKD). Suitable rehabilitation programs are needed to decrease disability and improve functionality to maintain independence in activities of daily life. AIMS: To assess the impact of CKD on the efficacy of rehabilitation in the geriatric population. METHODS: Retrospective single-center cohort study, demographic and clinical data of 190 elderly, non-dialysis dependent CKD patients, who underwent rehabilitation, during 2016-2020 were analyzed. RESULTS: Early CKD patients had longer duration of rehabilitation as compared with advanced CKD (32.6 ± 19.5 vs. 25.1 ± 17.6 days, p = 0.011) and tended to be more independent at discharge (37.2% vs. 27.9%, respectively; p < 0.001). Duration of rehabilitation, Mini-Mental State Examination (MMSE), Functional Independence Measurement (FIM) admission and estimated GFR were important predictors of FIM at discharge. Age was negatively correlated with admission FIM, eGFR, MMSE, and discharge FIM. The odds ratio for mortality among patients with advanced as compared to early CKD was 2.197 (CI 95% 1.159-4.166, p = 0.015). DISCUSSION: Existing rehabilitation programs raise questions of suitability for the consistently aging population, play an indispensable part in the goal of achieving functional independence in the elderly and should promote further investigation of the efficacy of rehabilitation for CKD patients. CONCLUSIONS: Advanced CKD was associated with lower FIM at admission and discharge, shorter duration of rehabilitation and more dependence at discharge, as compared to patients with early CKD. Implementing a multidisciplinary team, focused on the specific needs of geriatric CKD patients, with clear, objective parameters and goals may lead to better rehabilitative outcomes, with decreased public and private costs of ongoing care.

Clinical Outcomes of Vascular Accesses in Hemodialysis Patients.

BACKGROUND: Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable. OBJECTIVES: To assess possible predictors of primary and secondary failure of vascular access. METHODS: This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up. RESULTS: A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure. CONCLUSIONS: Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.

The Combined Prognostic Significance of Alkaline Phosphatase and Intracranial Arterial Calcifications in Hemodialysis Patients.

INTRODUCTION: The prevalence of intracranial arterial calcification (ICAC) in maintenance hemodialysis (MHD) patients is about 90%, and its severity is correlated with age, hemodialysis vintage, and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient for medial calcification because of inhibition by pyrophosphate. Alkaline phosphatase (ALP) promotes calcification by hydrolyzing extracellular pyrophosphate. Epigenetic mechanisms involving ALP inhibition by apabetalone were investigated as a potential target for preventing vascular calcifications (VCs). This study assessed the combined impact of VCs and elevated serum ALP on mortality among chronic HD patients. METHODS: VCs represented by ICAC were measured simultaneously with mineral bone disease parameters including serum ALP of MHD patients who underwent noncontrast brain computed tomography from 2015 to 2018 in our institution. RESULTS: This retrospective study included 150 MHD patients (mean age 71.3 ± 12.1 years, 60.1% male). Of the total cohort, 12 (7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95% CI: 1.7-12.7) among patients with brain calcifications and normal ALP (p = 0.003) and odds ratios for all-cause mortality of 6.1 (95% CI: 2.1-17.7) among patients with brain calcifications and elevated ALP (p= 0.001). CONCLUSION: We found an independent association between ICAC and the risk of death among MHD patients. The combined effect of ICAC and elevated ALP was associated with a higher odds ratio for all-cause mortality in MHD patients and may contribute to the risk stratification of these patients.

Enhanced expression of Galectin-3 in gestational diabetes.

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications. METHODS AND RESULTS: Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar. CONCLUSION: Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet.

Assessment of the CHA2DS2-VASc Score in Predicting Mortality and Adverse Cardiovascular Outcomes of Patients on Hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis are at high mortality and cardiovascular risk. This study was aimed to assess whether the CHA2DS2-VASc score may be used for risk stratification of this population. METHODS: Included were patients undergoing chronic hemodialysis at Meir Medical Center. The CHA2DS2-VASc score was calculated for each patient at the initiation of hemodialysis. Patients were classified into 3 groups according to the CHA2DS2-VASc score: 0-3 (low), 4-5 (intermediate), and ≥6 (high). The primary endpoint was the composite of all-cause mortality, myocardial infarction, and stroke during the first year of hemodialysis. RESULTS: Of the 457 patients with ESRD, 181 (40%) had low, 193 (42%) intermediate, and 83 (18%) high CHA2DS2-VASc scores. During the first year of hemodialysis, 109 (23.8%) patients died, 17 (3.7%) had a stroke, and 28 (6.1%) had a myocardial infarction. Compared to patients in the low CHA2DS2-VASc score group, those in the intermediate and high score groups had higher risk for the composite endpoint (OR: 2.6, 95% CI: 1.6-4.2, p < 0.01 and OR: 4.2, 95% CI: 2.3-7.5, p < 0.01, respectively). Each 1-point increase in CHA2DS2-VASc score was associated with a 38% increased risk for the composite endpoint, a 19% increased risk for 1-year myocardial infarction, and a 29% increased risk for 1-year stroke. CONCLUSIONS: Patients with ESRD are at an extremely high mortality and cardiovascular risk within the first year of hemodialysis. The CHA2DS2-VASc score was strongly associated with adverse outcomes and may be used for risk stratification of these patients.

Elevated Circulating Cell-Free DNA in Hemodialysis-Treated Patients Is Associated with Increased Mortality.

BACKGROUND: Predicting the mortality risk of patients un-dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. METHODS: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. RESULTS: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1-3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. CONCLUSIONS: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.

Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes.

To evaluate changes in the inflammatory response of thioredoxin (TXN), thioredoxin interacting protein (TXNIP), transducer and activator of transcription 3, NFƙB-p50 and STAT3 at the level of maternal serum, placenta, and umbilical cord blood of women with gestational diabetes mellitus type 2 (GDMA2) compared to normal pregnancies (NP). Thirty pregnant women (20 with GDMA2 and 10 NP) were recruited during admission for delivery. Blood samples were obtained from the parturients and umbilical cords, as well as placental tissue for mRNA and protein extraction. TXNIP mRNA expression was significantly increased in maternal serum of women with GDMA2 compared to NP women. TXNIP mRNA was significantly decreased in GDMA2 placentas and cord blood compared to NP. TXN/TXNIP mRNA ratio showed significantly high absolute values in placental and cord blood (2.39 and 1.66) respectively, compared to maternal ratio (1.084) (P < 0.001). TXN/TXNIP placenta protein ratio showed similar values between GDMA2 and NP (0.98 and 0.86; P = 0.7). STAT3 and its target protein SOCS3, as well as NFƙB-p50 mRNA expression were significantly increased in placentas of GDMA2. NFƙB-p50 mRNA expression was significantly decreased in cord blood compared to both maternal and placental mRNA expression. Pro-inflammatory changes are expressed by low mRNA TXN/TXNIP ratio in maternal blood of GDMA2 patients, but not in placental and umbilical cord blood samples. This, as well as the feedback role of SOCS3 in STAT3 pathway and NFƙB-p50 expression, may indicate that the placenta has a role in protecting the fetus from damage due to inflammatory response, which is common in diabetes.

Gestational Diabetes Type 2: Variation in High-Density Lipoproteins Composition and Function.

Aims: Class A2 gestational diabetes mellitus (GDMA2) has short- and long-term effects on the mother and child. These may include abnormalities of placentation, damage to endothelial cells and cardiovascular disease. This research investigated the function and composition of high-density lipoproteins (HDL) among women with GDMA2 and their fetuses. Methods: Thirty pregnant women were recruited during admission for delivery. The function and expression of HDL, paraoxonase1 (PON1) and apolipoprotein A1 (APOA1) in the blood samples and the placental tissue were evaluated. The effect of HDL on migration of endothelial cells was measured in vitro. Results: Compared to normal pregnancy (NP), APOA1 in the maternal plasma of women with GDMA2 was decreased. More APOA1 and PON1 were released from HDL of women with GDMA2, compared to NP. Placental APOA1 and PON1 were decreased in GDMA2. For endothelial cells stimulated with TNFα, HDL cell migration was decreased when cells were evaluated with NP-HDL, as compared to GDMA2-HDL. Conclusions: GDMA2 affects the composition and function of HDL in plasma. Changes in HDL commonly seen in GDMA2 were observed in maternal and placental samples, but not in cord samples. These results might indicate a placental role in protecting the fetus by preserving the components and functions of HDL and require further investigation.

High-density lipoproteins (HDL) composition and function in preeclampsia.

PURPOSE: To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established. METHODS: Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression. RESULTS: PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL. CONCLUSIONS: HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.

Outcome of Idiopathic Membranous Nephropathy: A Retrospective Study.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in Caucasian adults. Most patients have good renal prognosis, but 30-40% may progress to end stage renal disease (ESRD). OBJECTIVES: To evaluate the efficacy and safety of immunosuppressive treatment (IST) in high-risk patients. METHODS: All IMN patients diagnosed by kidney biopsy from 2004-2010 were included. Clinical and laboratory data were collected at each follow-up visit. Risk assessment for renal progression classified patients as high risk if: 24 hour protein excretion > 6 g/day, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and severe disabling or life-threatening clinical symptoms of NS were present. RESULTS: Among 290 biopsies, 37 patients (12.7%) were IMN. They were allocated to the high-risk IST group (n=16) or low-risk supportive treatment (ST) group (n=21) according to the likelihood of developing renal failure. Mean follow-up was 47 ± 17.3 months. Complete and partial remission rate was 68.7% for high-risk IST vs. 90.4% for low-risk ST. In the high-risk IST group, eGFR was significantly lower at 30 months (65.5 ± 28.6 vs. 85.3 ± 21.6 at baseline, P < 0.05). Four high-risk patients reached ESRD. In the low-risk ST group, eGFR remained stable at 30 and 60 months. CONCLUSIONS: This study showed a high remission rate for IMN. IST with prednisolone and cyclophosphamide provided favorable renal outcomes in most high-risk patients. The very high remission rate obtained in the low-risk patients confirms the adequacy of supportive treatment in this group.

Anemia Management among Hemodialysis Patients with High Ferritin Levels.

BACKGROUND: Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists. OBJECTIVES: To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (< 500 ng/ml) ferritin levels. METHODS: In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation. RESULTS: Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period. CONCLUSIONS: Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.