Blood Thiol Redox State in Chronic Kidney Disease.

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.

Geriatric Nutritional Risk Index Is Predictive of Subjective Global Assessment and Dialysis Malnutrition Scores in Elderly Patients on Hemodialysis.

OBJECTIVE: Malnutrition is a frequent complication in patients on hemodialysis (HD), even if its adequate appraisal remains one of the most complicated challenges in the HD scenario because of the limits of current malnutrition biomarkers. The aim of our study was to assess the relation of subjective nutritional tools Subjective Global Assessment (SGA) and Dialysis Malnutrition Score (DMS) with the objective malnutrition tool Geriatric Nutritional Risk Index (GNRI) in elderly patients on HD. METHODS: This is a cross-sectional study involving 71 patients on maintenance HD. Mann-Whitney U and chi-square tests were used to compare data of male and female patients on HD. Linear and logistic regression models were used to assess the variables tested in all patients. RESULTS: GNRI was not different between male and female patients on HD, and it was negatively related to SGA and DMS: B, -0.05 (95% confidence interval, -0.08 to -0.02) P = 0.00 and B, -0.30 (95% confidence interval, -0.47 to -0.14) P = .00, respectively. Both continuous and categorical GNRI data were predictive of SGA = 3: Odds Ratio (OR), 0.74 (0.63 to 0.87) P = 0.00 and OR, 6.74 (1.54 to 29.45) P = 0.01, respectively. Similarly, GNRI data were related to DMS > 13: OR, 0.85 (0.76 to 0.85) P = 0.00 and 3.29 (1.08 to 10.05) P = 0.03, respectively. Continuous GNRI data remained significant in both male and female patients separately, whereas categorical GNRI data, only in male patients. CONCLUSIONS: GNRI is a reliable nutritional tool predictive of subjective malnutrition scores SGA and DMS, pointing out a relation between objective and subjective malnutrition indexes in both genders.

Integrated protocol for the prevention and treatment of skin ulcers in patients with end-stage renal disease.

Chronic Kidney Disease (CKD) is an escalating global health concern, affecting more than 10 % of the general population worldwide, amounting to over 800 million individuals. One of its major complications for patients is the high prevalence of skin ulcers . This study aims to develop a protocol for ulcer management within the context of a hospital-based dialysis center. The success of this strategy is deeply rooted in the collaboration of a multidisciplinary team, continually enriched by specialist training. The clinical nurse specialist (CNS) in wound care plays a pivotal role in this approach. By employing a systematic methodology, the protocol is tailored to emphasize holistic care for patients diagnosed with end-stage renal disease undergoing hemodialysis. It accentuates the significance of proactive prevention, in-depth patient education, and the immediate identification of early wound signs. The research underscores the necessity to further weave in specialized training for ulcer care, ensuring each hospital visit is maximized for efficiency and effectiveness. Central to this protocol is the understanding that CKD is a growing concern, that the optimal management of ulcers relies heavily on multidisciplinary collaboration, and that an emphasis on prevention, patient education, and timely wound recognition is crucial to enhance patient care and experience.

Preliminary experience on the use of sucrosomial iron in hemodialysis: focus on safety, hemoglobin maintenance and oxidative stress.

PURPOSE: Iron is usually administered in hemodialysis patients by parenteral route, as oral absorption is poor due to high hepcidin levels. However, administrations of intravenous iron and iron overload are associated with high oxidative stress and systemic inflammation that can affect patient survival. With this study, we evaluated an alternative type of oral iron for the treatment of anemia in hemodialysis patients. The formulation consists in ferric pyrophosphate covered by phospholipids plus sucrose ester of fatty acid matrix, named sucrosomial iron, whose absorption is not influenced by hepcidin. METHODS: Twenty-four (24) patients undergoing chronic hemodialysis switched iron supplementation from intravenous (ferric gluconate 62.5 mg weekly) to oral (sucrosomial iron, 90 mg weekly in 3 administrations of 30 mg) route for 3 months. Classical anemia, iron metabolism, inflammation and nutritional biomarkers were monitored, as well as biomarkers of oxidative stress, such as protein-bound di-tyrosines, protein carbonylation, advanced oxidation protein products and protein thiols. RESULTS: Over the 3 months, hemoglobin values remained stable, as the values of hematocrit and mean corpuscular volume. In parallel, other anemia parameters dropped, including ferritin, transferrin saturation and serum iron. On the other side, nutritional biomarkers, such as total proteins and transferrin, increased significantly during the time frame. We also observed a significant decrease in white blood cells as well as a non-significant reduction in C-reactive protein and some oxidative stress biomarkers, such as protein carbonyls and di-tyrosines. CONCLUSION: Our study demonstrates that a therapy with sucrosomial iron in hemodialysis patients is safe and can maintain stable hemoglobin levels in a three-month period with a possible beneficial effect on oxidative stress parameters. However, the reduction of ferritin and transferrin saturation suggests that a weekly dosage of 90 mg is not sufficient in hemodialysis patients in the long time to maintain hemoglobin.

mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients.

SARS-CoV-2 vaccination has proven effective in inducing an immune response in healthy individuals and is progressively us allowing to overcome the pandemic. Recent evidence has shown that response to vaccination in some vulnerable patients may be diminished, and it has been proposed a booster dose. We tested the kinetic of development of serum antibodies to the SARS-CoV-2 Spike protein, their neutralizing capacity, the CD4 and CD8 IFN-γ T-cell response in 328 subjects, including 131 immunocompromised individuals (cancer, rheumatologic, and hemodialysis patients), 160 health-care workers (HCW) and 37 subjects older than 75 yr, after vaccination with two or three doses of mRNA vaccines. We stratified the patients according to the type of treatment. We found that immunocompromised patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines. However, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody. Similarly to HCW, previously infected and vaccinated immunocompromised individuals demonstrate a stronger SARS-CoV-2-specific immune response than those who are vaccinated without prior infection.

Different cardiovascular responses to hemodialysis-induced fluid depletion and blood pressure compliance.

BACKGROUND: On the basis of cardiovascular compliance, hemodialysis (HD) patients can be classified as hypotension prone (HP) or hypotension resistant (HR). METHODS: We compare the hemodynamic behavior and myocardial performances in 6 HP and 6 HR patients before and after an isolated ultrafiltration (IU) session removing 3% of total body water. RESULTS: HP show higher basal plasma angiotensin II levels during IU (p<0.01), whereas angiotensin II remained unchanged in HR patients (p<0.001 between groups). The percentage changes of plasma volume (PV) was similar in the 2 groups. A significant reduction of cardiac index was observed only in the HP group (p<0.001 between groups). The mean values of heart rate remained significantly higher, whereas total peripheral resistances significantly fell in the HP in comparison with the HR group (p<0.001 between groups). During IU, the mean arterial pressure (MAP) changes were -10 +/- 3 mm Hg in the HP vs. -3.3 +/- 2 mm Hg in the HR group (p<0.001). Echocardiography data were collected before and after IU. All enrolled patients presented left ventricular hypertrophy; following IU, HP patients showed a reduction of mean left ventricular diameter (p<0.01), left atrial diameters and right atrial diameter, and a change in percentage of right atrium ejection fraction (p<0.001, p<0.01). CONCLUSIONS: In comparison with HR patients, HP patients before and after IU showed a defective arteriovenous tone adjustment to the PV changes, with a hemodynamic picture of abnormal sympathetic stimulation. Moreover, a reduced cardiac preload with both atrial and ventricular underfilling in these patients is at risk for a sudden drop in MAP.

Plasma Protein Carbonyls as Biomarkers of Oxidative Stress in Chronic Kidney Disease, Dialysis, and Transplantation.

Accumulating evidence indicates that oxidative stress plays a role in the pathophysiology of chronic kidney disease (CKD) and its progression; during renal replacement therapy, oxidative stress-derived oxidative damage also contributes to the development of CKD systemic complications, such as cardiovascular disease, hypertension, atherosclerosis, inflammation, anaemia, and impaired host defence. The main mechanism underlying these events is the retention of uremic toxins, which act as a substrate for oxidative processes and elicit the activation of inflammatory pathways targeting endothelial and immune cells. Due to the growing worldwide spread of CKD, there is an overwhelming need to find oxidative damage biomarkers that are easy to measure in biological fluids of subjects with CKD and patients undergoing renal replacement therapy (haemodialysis, peritoneal dialysis, and kidney transplantation), in order to overcome limitations of invasive monitoring of CKD progression. Several studies investigated biomarkers of protein oxidative damage in CKD, including plasma protein carbonyls (PCO), the most frequently used biomarker of protein damage. This review provides an up-to-date overview on advances concerning the correlation between plasma protein carbonylation in CKD progression (from stage 1 to stage 5) and the possibility that haemodialysis, peritoneal dialysis, and kidney transplantation improve plasma PCO levels. Despite the fact that the role of plasma PCO in CKD is often underestimated in clinical practice, emerging evidence highlights that plasma PCO can serve as good biomarkers of oxidative stress in CKD and substitutive therapies. Whether plasma PCO levels merely serve as biomarkers of CKD-related oxidative stress or whether they are associated with the pathogenesis of CKD complications deserves further evaluation.

Subjective Global Assessment-Dialysis Malnutrition Score and arteriovenous fistula outcome: A comparison with Charlson Comorbidity Index.

INTRODUCTION:: Malnutrition is a well-recognized risk factor for all-cause mortality in hemodialysis patients. However, its role for arteriovenous fistulas outcome has not been exhaustively investigated. Our aim was to point out the impact of Subjective Global Assessment-Dialysis Malnutrition Score as independent predictor of arteriovenous fistulas thrombosis (vascular access thrombosis) and/or significant stenosis (vascular access stenosis). In addition, we compared it with the widespread Charlson Comorbidity Index. METHODS:: We assessed 57 hemodialysis patients for a 2-year interval and evaluated the incidence of vascular access thrombosis and/or stenosis. Linear regression analysis was used to test the relation of variables with Subjective Global Assessment-Dialysis Malnutrition Score at baseline. Logistic and Cox regression analysis evaluated markers as predictors of both vascular access thrombosis and stenosis. Receiver operating characteristic curve analysis was used to compare area under the curve values of Subjective Global Assessment-Dialysis Malnutrition Score, Charlson Comorbidity Index, and modified Charlson Comorbidity Index. RESULTS:: Age and Charlson Comorbidity Index were positively related to Subjective Global Assessment-Dialysis Malnutrition Score: B = 0.06 (95% CI = 0.01; 0.11) and B = 0.31 (95% CI = 0.01; 0.63). Higher albumin and normalized protein catabolic rate levels had a protective role against vascular access failure: OR = 0.67 (95% CI = 0.56; 0.81) and OR = 0.46 (95% CI = 0.32; 0.67), respectively. Higher Subjective Global Assessment-Dialysis Malnutrition Score and Charlson Comorbidity Index values were significant risk factors: HR = 1.42 (95% CI = 1.04; 1.92) and HR = 1.48 (95% CI = 1.01; 2.17), respectively. Area under the curve of Subjective Global Assessment-Dialysis Malnutrition Score was significantly higher than those of both Charlson Comorbidity Index and modified Charlson Comorbidity Index: 0.70 (95% CI = 0.50; 0.88) versus 0.61 (95% CI = 0.41; 0.80) and 0.55 (95CI% = 0.41; 0.70). CONCLUSION:: Subjective Global Assessment-Dialysis Malnutrition Score, as well as Charlson Comorbidity Index, are useful tools to predict vascular access failure and should be carefully and periodically evaluated in order to check significant variations that may compromise vascular access survival.

Advanced oxidation protein products in nondiabetic end stage renal disease patients on maintenance haemodialysis.

In chronic kidney disease (CKD), the impairment of the excretory function leads to elevation in the blood concentrations of urea, creatinine, and various protein metabolic products. Advanced oxidation protein products (AOPP), along with protein carbonyls, protein-bound di-tyrosines and S-thiolated proteins, are considered biomarkers of oxidative stress in end-stage renal disease (ESRD) patients on maintenance haemodialysis (HD). In this study, we evaluated the correlations between plasma levels of AOPP (measured by size exclusion/gel filtration high performance liquid chromatography) and those of protein-bound di-tyrosines, protein carbonyls, albumin and fibrinogen in 50 nondiabetic ESRD patients on maintenance HD. Considering that AOPP could represent the bridge between oxidative stress and inflammation, having been identified as proinflammatory mediators, we also evaluated the association between AOPP levels, C-reactive protein concentration and white blood cells count. Finally, we assessed the associations between plasma level of AOPP and serum concentrations of creatinine and urea, both of which showed a strong dependence on the chronological age of haemodialysed patients. Taken together, our results confirm the robust relationship between uraemia and oxidative stress, especially when measured as biomarkers of severe protein oxidative damage (e.g. plasma AOPP).

Cytapheresis in inflammatory bowel diseases: current evidence and perspectives.

Ulcerative colitis and Crohn's disease are inflammatory bowel diseases with a chronic relapsing course. Management of both conditions is far from being fully satisfactory. For this reason in the last decade a large number of biological therapies, targeting cytokines involved in intestinal inflammation, has been developed with various results in terms of efficacy, safety and costs. Activated granulocytes and monocytes represent the major sources of pro-inflammatory cytokines in the intestinal mucosa, playing a pivotal role in inducing and maintaining intestinal inflammation. Leukocytapheresis using an adsorptive carrier-based system (Adacolumn) or a removal filter column (Cellsorba) has been proposed as a feasible, safe and effective therapy for ulcerative colitis and Crohn's disease. The objective of this paper is to provide an overview on the current knowledge about mechanisms of action, available clinical data and the possible future perspectives for the use of Adacolumn and Cellsorba in the management of inflammatory bowel diseases.

SGLT1 and SGLT1 Inhibitors: A Role to Be Assessed in the Current Clinical Practice.

Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential. At present, whereas the SGLT2 inhibitors are widely applied in current clinical practice as an effective and well-tolerated treatment that increases the urinary excretion of glucose, less is known about the use of SGLT1 inhibitors. SGLT1s are of primary importance in the small intestine, an organ that does not express SGLT2, while in the kidney they are expressed in the late renal proximal tubules, where it reabsorbs the glucose escaped from the upstream SGLT2. Hence, SGLT1-mediated glucose reabsorption in the kidney is increased when the tubular glucose load overwhelms the capacity of SGLT2 or when the latter is inhibited. The role of SGLT1 in intestinal and renal glucose transport makes the transporter a potential target for antidiabetic therapy. Here, we briefly report the evidence on LX2761, a new inhibitor against SGLT1 and SGLT2 in vitro, which acts in vivo as a selective inhibitor of SGLT1 in the gastrointestinal tract. LX2761 improves glycemic control without the glycosuria-related side effects of SGLT2 inhibitors, particularly genitourinary tract infections. However, whether it represents a valid therapeutic option for all patients with diabetes or is more appropriate for specific phenotypes, e.g., patients with concomitant diabetes and chronic kidney disease, who may benefit less from the renal mechanism of selective SGLT2 inhibitors, remains to be tested in large randomized controlled trials.

Subjective Global Assessment-Dialysis Malnutrition Score and cardiovascular risk in hemodialysis patients: an observational cohort study.

BACKGROUND: Malnutrition is an important risk factor for cardiovascular mortality in hemodialysis (HD) patients. However, current malnutrition biomarkers seem unable to accurately estimate the role of malnutrition in predicting cardiovascular risk. Our aim was to investigate the role of the Subjective Global Assessment-Dialysis Malnutrition Score (SGA-DMS) compared to two well-recognized comorbidity scores-Charlson Comorbidity Index (CCI) and modified CCI (excluding age-factor) (mCCI)-in predicting cardiovascular events in HD patients. METHODS: In 86 maintenance HD patients followed from June 2015 to June 2017, we analyzed biohumoral data and clinical scores as risk factors for cardiovascular events (acute heart failure, acute coronary syndrome and stroke). Their impact on outcome was investigated by linear regression, Cox regression models and ROC analysis. RESULTS: Cardiovascular events occurred in 26/86 (30%) patients during the 2-year follow-up. Linear regression showed only age and dialysis vintage to be positively related to SGA-DMS: B 0.21 (95% CI 0.01; 0.30) p 0.05, and B 0.24 (0.09; 0.34) p 0.02, respectively, while serum albumin, normalized protein catabolic rate (nPCR) and dialysis dose (Kt/V) were negatively related to SGA-DMS: B - 1.29 (- 3.29; - 0.81) p 0.02; B - 0.08 (- 1.52; - 0.35) p 0.04 and B - 2.63 (- 5.25; - 0.22) p 0.03, respectively. At Cox regression analysis, SGA-DMS was not a risk predictor for cardiovascular events: HR 1.09 (0.9; 1.22), while both CCI and mCCI were significant predictors: HR 1.43 (1.13; 1.87) and HR 1.57 (1.20; 2.06) also in Cox adjusted models. ROC analysis reported similar AUCs for CCI and mCCI: 0.72 (0.60; 0.89) p 0.00 and 0.70 (0.58; 0.82) p 0.00, respectively, compared to SGA-DMS 0.56 (0.49; 0.72) p 0.14. CONCLUSIONS: SGA-DMS is not a superior and significant prognostic tool compared to CCI and mCCI in assessing cardiovascular risk in HD patients, even it allows to appraise both malnutrition and comorbidity status.

Plasma Protein Carbonylation in Haemodialysed Patients: Focus on Diabetes and Gender.

Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience oxidative/carbonyl stress, which is postulated to increase after the HD session. The influence of diabetes mellitus and sex on oxidation of plasma proteins in ESRD has not yet been clarified despite that diabetic nephropathy is the most common cause of ESRD in developed and developing countries and despite the increasingly emerging differences between males and females in epidemiology, pathophysiology, clinical manifestations, and outcomes for several diseases. Therefore, this study aimed to evaluate the possible effect of type 2 diabetes mellitus, gender, and dialysis filter on plasma level of protein carbonyls (PCO) in ESRD patients at the beginning and at the end of a single HD session. Results show that mean post-HD plasma PCO levels are significantly higher than mean pre-HD plasma PCO levels and that the type of dialysis filter and dialysis technique are unrelated to plasma PCO levels. The mean level of plasma PCO after a HD session increases slightly but significantly in nondiabetic ESRD patients compared to diabetic ones, whereas it increases more markedly in women than in men. These novel findings suggest that women with ESRD are more susceptible than men to oxidative/carbonyl stress induced by HD.

Role of the kidney in plasma cytokine removal in sepsis syndrome: a pilot study.

BACKGROUND: At the onset of sepsis, endotoxins or other components of the gram-negative capsular wall stimulate the synthesis of pro-inflammatory cytokines by activating the monocyte-macrophage system. In this context, interleukin-1 beta (IL-1), tumor necrosis factor-alpha (TNF) and IL-6 are considered co-responsible for the clinical picture of sepsis syndrome. Many organs can be involved, and kidney dysfunction occurs early with a picture of non-oliguric acute renal failure (NOARF) or oliguric acute renal failure (OARF). This study aimed to investigate the role of the kidney in plasma removal of some pro-inflammatory cytokines in the first 24 hr after the diagnosis of sepsis syndrome, when, according to the peak concentration hypothesis, their plasma concentration is maximal. 18 septic patients, six patients with normal renal function (NRF), six with NOARF and six with OARF were selected for the study. We measured the plasma levels and urinary excretion of IL-1, TNF and IL-6 at the moment of sepsis diagnosis (base-line) and 24 hr later. Moreover, urinary excretion of IL-1 and IL-6 was done in the same interval by measuring the percentage of fractional excretion (FE%) of these cytokines. RESULTS: Multivariate analysis (ANOVA) showed no significant difference in plasma IL-1 levels at baseline in the NRF, NOARF and OARF patients (p=0.11), whereas a significant increase was found in OARF patients at 24 hr, p<0.023. OARF patients presented significantly higher IL-6 plasma levels compared with the other two groups, both at baseline (p<0.0002) and at 24 hr (p<0.0001). Plasma TNF levels were not significantly different at baseline (p=0.184), whereas the OARF group showed a significant increase at 24 hr, (p<0.05). The urinary FE of IL-1 was 1.2 +/- 0.6% in NRF, and 1.0 +/- 0.4% in NOARF (ns), the FE of IL-6 was 1.4 +/- 0.8% in NRF and 1.3 +/- 0.3% in NOARF (ns). A negative in-significant correlation was found between the plasma concentration and FE of IL-1 beta (r=-0.33, p<0.07). Urinary excretion of IL-6 was significantly related with urinary IL-1 beta, both expressed as pg/ml/mg of urinary creatinine (r=0.85, p<0.0001). No significant relation was found between IL-1 and IL-6 plasma concentrations or between plasma concentration and FE of IL-6. CONCLUSION: These results suggest that at disease onset, the kidney removes some pro-inflammatory cytokines from the plasma of septic patients until diuresis is preserved. As it has been demonstrated that NOARF patients have a better prognosis than OARF patients and their survival in sepsis syndrome seems to be inversely related to the plasma pro-inflammatory cytokine levels, diuresis maintenance by diuretic infusion can be important to improve patient prognosis.

Pregnancy in lupus nephritis.

BACKGROUND: Fetal and maternal outcomes of 70 pregnancies in 48 women with lupus nephritis were retrospectively analyzed. METHODS: In 13 women, lupus nephritis developed during pregnancy (group A). In 38 patients with known lupus nephritis (including 3 patients in group A who had another pregnancy), 57 pregnancies occurred. In 6 patients, a therapeutic abortion was performed. The remaining 51 pregnancies were considered pregnancies in lupus nephritis (group B). RESULTS: Fetal loss was 36% (38%, group A; 35%, group B); it decreased from 46% in the 1970s to 30% in the last decade. Among 41 live births, there were 13 preterm deliveries and 28 full-term deliveries. At multivariate analysis, proteinuria (P = 0.025), arterial hypertension (P = 0.05), and antiphospholipid antibodies (P = 0.01) were independent predictors of fetal loss. In group A, 3 patients developed acute renal failure, irreversible in 1 patient (7.7%); all other patients recovered after steroid and immunosuppressive therapy. In group B, 12 renal flares and 1 extrarenal flare developed during pregnancy or the postpartum period. Two patients progressed to irreversible renal failure (3.9%), and 1 of the 2 patients died. All other patients recovered. The incidence of renal flares before or during pregnancy was not different (P = 0.51). Renal quiescence at the onset of pregnancy was the only predictor of favorable maternal outcome. CONCLUSION: Proteinuria, hypertension, and positivity of antiphospholipid antibodies are independent predictors of adverse fetal outcome. Quiescence of renal disease is the only predictor of favorable maternal outcome.

Epidemiology of GB virus c/hepatitis g virus infection in patients on peritoneal dialysis.

BACKGROUND: A new genus in the family Flaviviridae has recently been discovered; it has provisionally been designated GBV-C/HGV. As determined by virologic techniques [reverse-transcription polymerase chain reaction (RT-PCR)], infection with GBV-C/HGV is frequent in renal transplant (RT) recipients and in patients on chronic hemodialysis (HD). The epidemiology of GBV-C/HGV infection in patients on peritoneal dialysis is scarce and mostly based on RT-PCR technology. PURPOSE: We report on the prevalence (as detected by serologic and virologic techniques) and the risk factors for GBV-C/HGV infection in a cohort of patients on continuous ambulatory peritoneal dialysis (CAPD). We also tested a control group of blood donors. METHODS: Infection by GBV-C/HGV was assessed by serologic and virologic techniques. Cases of GBV-C/HGV viremia (GBV-C/HGV RNA) were detected by RT-PCR. Antibodies to the envelope protein of GBV-C/HGV (anti-E2 GBV-C/HGV antibody) were analyzed by serologic methods. RESULTS: We found a high frequency [17/85 (20%)] of GBV-C/HGV. The rates of GBV-C/HGV viremia and anti-E2 GBV-C/HGV positivity were 10.5% (9/85) and 10.5% (9/85) respectively. In most patients [17/18 (94%)], the presence of anti-E2 GBV-C/HGV antibody was associated with clearance of GBV-C/HGV from serum. No relationship was noted between anti-E2 GBV-C/HGV antibody (or GBV-C/ HGV viremia) and age, sex, race, time on dialysis, anti-HCV antibody, HBsAg status, and anti-HIV positivity. The frequency of GBV-C/HGV infection in CAPD patients was much higher than that in blood donors, even if the difference did not approach statistical significance. No associations between GBV-C/HGV positivity and biochemical liver tests [aminotransferase and gamma glutamyl transpeptidase (GGT)] were apparent. CONCLUSIONS: Infection by GBV-C/HGV as detected by RT-PCR and anti-E2 antibody was common in patients on CAPD and in controls alike. No association was seen between GBV-C/HGV and various demographic or clinical factors. The clinical significance of GBV-C/HGV in CAPD remains unclear. Larger investigations are in progress.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients.

INTRODUCTION: Hemodialysis (HD)-induced inflammation has a pathogenetic role in patients with end-stage renal disease (ESRD). The aim of the present study was to assess whether pentraxin-3 (PTX3) could be a reliable biomarker of HD-induced inflammation and of membrane biocompatibility. METHODS: We prospectively enrolled 31 HD patients. Blood samples for determining PTX3, C-reactive protein (CRP), leukocytes and neutrophils were drawn from the arterial needle, before dialysis after the long dialysis-free interval (time 0), at the end of the index session (time 1) and before the next dialysis session (time 2). In 22 of 31 patients, 30 minutes after start of dialysis, PTX3 and CRP plasma levels were measured in blood collected from both the arterial and venous lines (time A - time V) of the dialyzer. In 7 of 22 patients intracellular PTX3 levels in neutrophils were measured at the end of session. RESULTS: PTX3 venous levels were significantly increased at the end of the index session compared with baseline and in blood samples drawn from the venous line compared with the arterial line of the dialyzer. At time 1, a reduction of intracellular PTX3 in neutrophils was noticed. In contrast, CRP plasma levels were stable during the HD session. CONCLUSIONS: Our findings suggest that PTX3, which is rapidly produced by several cell types and released by neutrophils upon stimulation, could be a biomarker of HD-induced inflammation and of blood-membrane bioincompatibility.

Inter-day glycemic variability assessed by continuous glucose monitoring in insulin-treated type 2 diabetes patients on hemodialysis.

BACKGROUND: Type 2 diabetes patients on chronic hemodialysis have a high prevalence of cardiovascular complications and often show a poor glycemic control. Single-spot glycemic measurements are not always meaningful, and the hemoglobin A1c (HbA1c) value does not reflect short-term variations in glucose metabolism in this patient category. Therefore, to better understand their metabolic balance, we studied a group of diabetes patients on hemodialysis by a continuous glucose monitoring (CGM) system. METHODS: Twelve insulin-treated type 2 diabetes patients on hemodialysis were studied by a microdialysis-based subcutaneous glucose sensor over a period of 2 days, including the dialysis day (HD) and the following inter-dialytic period ("free" day [FD]). RESULTS: The mean 24-h glycemic value, the mean amplitude of glucose excursions, and the SD of mean glucose were significantly higher in the HD than the FD (186 ± 50 vs. 154 ± 25 mg/dL, P<0.05; 75 ± 22 vs. 56 ± 15 mg/dL, P<0.05; and 57 ± 6 vs. 35 ± 11 mg/dL, P<0.05, respectively). Considering the 48-h recording, there was a direct correlation between the mean glucose concentration and the HbA1c (r=0.47, P<0.05), whereas no association was observed between the measures of glucose variability and HbA1c. CONCLUSIONS: Insulin-treated diabetes patients on hemodialysis showed different glucose profiles between the HD and the FD. In particular, in the HD they have had an increased glycemic variability, which may represent an adjunctive risk factor for cardiovascular complications. Therefore the use of a CGM system, as a means of assessing the measures of glycemic variability, could improve the management of insulin therapy in these patients.